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I'M WINN ARIAS AND WE WELCOME 

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YOU TO THE THIRD YEAR OF THE DE 

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DEMYSTIFYING MEDICINE AT THE 

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NATIONAL INSTITUTES OF HEALTH.

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THIS IS TO BRIDGE THE EXCITING 

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DEVELOPMENTS IN BIOLOGY, 

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ENGINEERING AND COMPUTER 

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SCIENCES WITH MEDICINE.

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THIS TAKES MANY FORMS.

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WE HAVE REACHED THIS ISSUE IN 

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SPACE AT THE BOTTOM OF THE SEA 

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AND ORIGIN OF LIFE AND TODAY IN 

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A MORE TRADITIONAL WAY WE ARE 

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CONCERNED WITH A DISEASE DISEASE

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AND THE BRIDGING IS BETWEEN THE 

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CLINICAL, THERAPEUTIC AND BASIC 

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UNDERLYING SCIENCE OF THE 

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DISEASE ITSELF.

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DEMYSTIFYING MEDICINE MEETS 

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EVERY TUESDAY FROM 4:00 TO 6:00 

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FROM JANUARY TO THE MIDDLE OF 

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PAY.

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-- MAY.

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YOU CAN WATCH IT USING THE LINK 

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THAT'S PRESENT ON THE SLIDE THE 

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CME CREDIT WAS LISTED AS 52088 

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AND ENCOURAGE MANY IN THIS 

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COUNTRY AND ABROAD TO COMMIT 

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QUESTIONS CLICKING ON THE SEND 

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LIVE FEEDBACK ON YOUR COMPUTER 

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OR SEND IT BY VIDEOCAST.

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I WOULD BRING YOUR ATTENTION TO 

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ALL PREVIOUS SESSIONS FOR THE 

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PAST 25 YEARS ARE ARCHIVED AND 

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THE LINK IS SHOWN HERE.

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IF YOU HAVE ADDITIONAL QUESTIONS

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GET IN TOUCH.

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THE LOGO IS THE BROOKLYN BRIDGE 

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AND THE TWO PEOPLE ON THE 

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SIDEWALK OR CAT WALK ARE 

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DISCUSSING TWO DIFFERENT 

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ASPECTS, TWO SILOS, IF IT WERE.

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SO TODAY THE SILOS ARE 

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REPRESENTED BY GENETIC AND 

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THERAPEUTIC ASPECT.

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WE'RE EXTREMELY FORTUNATE TO 

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HAVE THREE PRESENTERS TODAY.

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THE FIRST IS LESLIE GORDON A 

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PROFESSOR OF PEED RICKS AT THE 

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ALBERT MEDICAL SCHOOL AT BROWN 

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UNIVERSITY IN PROVIDENCE, RHODE 

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ISLAND.

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SHE IS THE CO-FOUNDER AND 

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MEDICAL DIRECTOR OF THE RESEARCH

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FOUNDATION.

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SHE IS DESIGNED AND IMPLEMENTED 

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SEVERAL CLINICAL TRIALS FOR 

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PROGERIA WITH VARIOUS COLLEAGUES

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IN BOSTON AND HAS DEVELOPED AN 

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OBJECTIVE CLINICAL BIOMEDICAL 

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THAT CAN BE USED TO ASSESS EYE 

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THERAPEUTIC RESPONSE.

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HER SON, SAM BURNS WAS BORN IN 

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1998 WITH PRO GERRIA AND RECALL 

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YOUR ATTENTION TO A REMARKABLE 

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2013 TED TALK SHE PROVIDED.

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OUR SECOND SPEAKER OR 

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PARTICIPANT IS WELL BUT A BRIEF 

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INTRODUCTION AND FRANCIS COLLINS

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IS A GLOBAL LEADER RESEARCH AND 

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POLICY HE FOUND THE GENES FOR 

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CYSTIC FIBROSIS, NEURAL FIBR

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FIBROMATOSIS AND CAME TO THE NIH

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TO HEAD THE HUMAN GENOME PROJECT

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WHICH BECAME THE HUMAN GENOME 

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RESEARCH INSTITUTE AT WHICH THE 

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HUMAN GENOME WAS SEQUENCED.

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HE IS THE LONGER SERVING 

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DIRECTOR AT THE NIH FROM 2009 TO

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2022 UNDER THREE PRESIDENTS.

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HE'S INITIATED MAJOR PROJECTS 

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SOME OF WHICH ARE LISTED ON THE 

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SLIDE HERE.

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THEY COVER FUNDAMENTAL SCIENCE 

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TO CLINICAL ASPECTS.

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HE'S ALSO VERY ACTIVE IN THE 

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DEVELOPMENT OF GLOBAL PROGRAMS 

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PARTICULARLY RELATED TO HIV AND 

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MORE RECENTLY TO HEPATITIS C.

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IN THE GOVERNMENT, HE'S BEEN THE

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PRESIDENT'S ACTING SCIENCE 

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ADVISER AND CO-CHAIR WITH THE 

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SCIENCE TECHNOLOGY COUNCIL.

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FRANCIS HAS BEEN AWARDED 

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ENUMERABLE PRIZES AND AWARDS FOR

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HIS EXEMPLARY LEADERSHIP.

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THE MOST NOTED ARE MEMBER OF THE

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NATIONAL ACADEMY OF MEDICINE AND

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SCIENCE AND NATIONAL MEDAL OF 

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FREEDOM AND NATIONAL MEDAL OF 

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SCIENCE AND ELECTED TO THE ROYAL

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SOCIETY.

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IN 2002 HE HAS BEEN WORKING EVEN

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THROUGH THE PERIOD OF HIS NIH 

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LEADERSHIP SEARCHING FOR GENES 

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FOR DIABETES MELLITUS TYPE II 

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AND THE SUBJECT OF TODAY'S 

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DISCUSSION THE 

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HUTCHINSON-GILFORD SYNDROME 

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KNOWN AS PROGERIA.

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THE TITLE IS PROGERIA A GENETIC 

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AND THERAPEUTIC ADVENTURE.

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THE FIRST SPEAKER IS LESLIE.

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>> THANK YOU FOR INVITING
US FOR

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THE TRIPLE TALK.

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WE'RE SO EXCITED.

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I DO WANT TO START BY 

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INTRODUCING ACTUALLY OUR THIRD 

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PRESENTER WHO HAS COME TO US 

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FROM ITALY ON ZOOM, SAMMY BASSO.

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I'VE KNOWN SAMMY SINCE HE WAS 5 

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AND HE'LL TELL YOU HIS STORY AND

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HE WAS VERY CLOSE WITH MY SON 

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SAM AND WE HAVE SORT OF GROWN 

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TOGETHER AS A FAMILY, OUR FAMILY

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AND HIS FAMILY AND I CAN TELL 

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YOU THAT HE IS ONE OF THE MOST 

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REMARKABLE PEOPLE I HAVE EVER 

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KNOWN.

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JUST AS ONE EXAMPLE, SAMMY WILL 

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TELL YOU HE HAS GROWN INTO 

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GETTING HIS ADVANCED DEGREE, HIS

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MASTERS IN THE SCIENCES AND 

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GENETICS AND HE HAD TO GO FOR
THAT FROM VENICE AREA AND TAKE A

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TRAIN TO THE ROME AREA AND 

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BECAUSE IT TOOK SO LONG ON THE 

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TRAIN HE WROTE A BOOK.

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AND THE BOOK IS THICK AND IT WAS

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PUBLISHED.

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THAT'S A TASTE OF WHAT SAMMY'S
LIKE.

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WHAT WE'RE GOING TO DO IS SHARE 

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OUR JOURNEY.

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WE'RE GOING TO TELL YOU WHERE WE

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ARE AND WHERE WE'RE GOING AND 

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WHERE WE'VE BEEN ON OUR ROAD TO 

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THE CURE FOR PROGERIA AND ALONG 

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THE WAY WE HOPE YOU CAN SEE HOW 

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OUR STORY CAN APPLY TO MILLIONS 

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AND MILLIONS OF PEOPLE.

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WE'RE GOING TO SHARE OUR 

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PERSPECTIVE FROM THREE TYPES OF 

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INTERRELATED STAKEHOLDERS AND 

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GET TO THE PATIENT AND FAMILY 

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PERSPECTIVES, FOUNDATIONAL 

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PROGRAM BUILDING PERSPECTIVES 

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AND THE BASIC AND CLINICAL 

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SCIENTIFIC DISCOVERY PERSPECTIVE

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AND THEY CANNOT BE MUTUALLY 

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EXCLUSIVE AND WE GO FROM SCIENCE

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TO CHATTING AND INTERVIEWS IN 

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CHATS AND QUESTIONS OF EACH 

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OTHER AND SO PLEASE SEND IN YOUR

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QUESTIONS BECAUSE WE MIGHT 

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ANSWER -- WE'RE GOING TO ANSWER 

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A FEW INTERSPERSED AND THEN 

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WE'LL GO BACK TO SCIENCE AND 

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THEN GO TO INTERVIEW.

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IT SHOULD BE PRETTY FUN.

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THIS IS WHO WE'RE FIGHTING FOR 

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AND MORE AND -- AND SOMETHING 

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I'M TALKING ABOUT MILLIONS OF 

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PEOPLE WHO HAVE RARE AND ULTRA 

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RARE DISEASES.

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THERE ARE MORE THAN 7,000 OF 

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THEM AND WE LEARN FROM EACH 

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OTHER WHEN WE SUCCEED.

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GET CALLS ALL TE TIME AND A CALL

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PEOPLE ALL THE TIME WHO ARE 

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DEALING WITH MOSTLY ULTRA RARE 

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BUT RARE DISEASES AS WELL.

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WE'RE TALKING ABOUT OVER 350 

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MILLION HUMAN BEINGS WHOSE LIVES

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ARE AT STAKE AND MOST DISEASES 

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ARE GENETIC AND MOST CHILDREN 

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WITH RARE DISEASES WILL DIE BY 

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THE TIME THEY'RE 5.

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PRETTY IMPACTFUL AND IMPACTS 

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THEIR LIVES AND THE LIVES OF 

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THEIR PARENTS, THEY'RE SIBLINGS 

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AND REVERBERATES THROUGH 

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FAMILIES AND COMMUNITIES.

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OUR STORY IS ONE OF MILLIONS AND

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WHEN WE SUCCEED I BELIEVE IT 

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WILL BE A SUCCESS AMONG MILLIONS

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AS WELL.

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WE JUST HAVE TO FIGURE OUT WHICH

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CAMERA WORKS.

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HI, SAMMY.

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WE'RE COMING TO YOU.

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>> THANK YOU.

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THIS IS BEAUTIFUL RACHEL AND A 

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SEQUENCE OF RACHEL BORN AS A 

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TODDLER, SECOND GRADE AND THEN 

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JUST THE WEEK BEFORE SHE TURNED 

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10 WHEN SHE PASSED AWAY FROM 

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HEART FAILURE.

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PROGERIA IS CALLED A SEGMENTAL 

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PREMATURE AGING DISEASE.

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IT'S NOT PASSED DOWN IN 

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FAMILIES.

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IT'S AUTOSOMAL DOMINANT, 

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SPORADIC AND CHILDREN WITH 

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PROGERIA DIE AT THE AVERAGE AGE 

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OF 14 1/2 BUT THERE'S A WIDE 

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RANGE AND THEY DIE OF PREMATURE 

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ATHEROSCLEROSIS WHICH IS THE 

217
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SAME DISEASE WHICH AFFECTS THE 

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REST OF US IN OUR '60s, '70s, 

219
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'80s AND '90s BUT HAPPENS FAST.

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IT AFFECTS OTHER BODY SYSTEMS 

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AND IT'S IMPORTANT TO UNDERSTAND

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NOT ONLY THE CLINICAL NATURAL 

223
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HISTORY OF THAT BUT WHAT THAT 

224
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MEANS BIO LOGICALLY ESPECIALLY 

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WHEN YOU'RE TRYING TO FIND 

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TREATMENTS AND CURE.

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THERE IS LOSS OF HAIR.

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THE CHILDREN ARE BORN LOOKING 

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NORMAL BUT HAVE FAILURE TO 

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THRIVE WHICH ARE LIFE LONG AND 

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VERY SMALL.

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THERE'S A LOSS OF SUB CUTANEOUS 

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BODY FAT AND BONY CONSEQUENCES.

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JOINT CONTRACT JURES.

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 -- CONTRACTURES AND MOST 

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IMPORTANTLY YOU'VE GOT THE 

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CARDIOVASCULAR DISEASE AND HERE 

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I'M SHOWING YOU WHAT THAT LOOKS 

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LIKE.

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THIS IS SHOWING YOU THE CAROTID 

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ARTERIES, BLOOD FLOWING UP FROM 

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THE BRAIN OVER HERE AND 

243
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COMPLETELY BLOCKED ON THE RIGHT 

244
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AND DOWN THE CONSEQUENCES OF 

245
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THAT THE WHITE AREA IS SHOWING 

246
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STROKE.

247
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HERE YOU'RE SEEING THE CROSS 

248
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SECTION OF THE AORTA.

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ALL OF THIS IS PLAQUE.

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IT'S HUGE.

251
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THIS IS A LAYER SUPPOSED TO BE 

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SUPER THIN MAKING FOR STIFF 

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VASCULATURE AS IT'S STIFF WHEN 

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IT'S TRYING TO PUSH BLOOD 

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AGAINST IT AND A CT SCAN OF A 

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15-YEAR-OLD WITH PROGERIA AND 

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ALL THIS WHITE IS CALCIUM.

258
00:13:39,193 --> 00:13:42,429
THIS IS THE AORTIC ARCH AND 

259
00:13:42,429 --> 00:13:46,200
DESCENDING AORTA AND DOES NOT 

260
00:13:46,200 --> 00:13:46,533
LOOK GOOD.

261
00:13:46,533 --> 00:13:52,339
THIS IS WHAT WE'RE UP AGAINST.

262
00:13:52,339 --> 00:13:57,778
I'LL TELL YOU A STORY THAT IS 

263
00:13:57,778 --> 00:13:59,313
VERY COMMON TO VERY RARE 

264
00:13:59,313 --> 00:13:59,646
DISEASES.

265
00:13:59,646 --> 00:14:03,650
WHEN SAM WAS 2 AND DIAGNOSED IN 

266
00:14:03,650 --> 00:14:05,352
1998 I HAD NEVER HEARD OF 

267
00:14:05,352 --> 00:14:07,654
PROGERIA AT ALL OR TAUGHT ABOUT 

268
00:14:07,654 --> 00:14:08,956
IT IN MEDICAL SCHOOL.

269
00:14:08,956 --> 00:14:10,691
THERE WERE ONLY A COUPLE 

270
00:14:10,691 --> 00:14:11,625
SCIENTISTS WORKING AT ALL 

271
00:14:11,625 --> 00:14:13,594
THROUGHOUT THE WORLD IN PROGERIA

272
00:14:13,594 --> 00:14:18,599
AND THERE WAS NOTHING OUT THERE.

273
00:14:18,599 --> 00:14:21,702
NO FUNDING, WE DIDN'T KNOW FIT 

274
00:14:21,702 --> 00:14:23,870
WAS A GENETIC DISEASE, HOW TO 

275
00:14:23,870 --> 00:14:25,205
TREAT IT, THE NATURAL HISTORY.

276
00:14:25,205 --> 00:14:27,341
THERE WAS NO PLACE FOR FAMILIES 

277
00:14:27,341 --> 00:14:28,742
AND PHYSICIAN TO GO.

278
00:14:28,742 --> 00:14:31,044
NO PLACE FOR TO US GO.

279
00:14:31,044 --> 00:14:33,413
AND THIS IS ESPECIALLY BACK THEN

280
00:14:33,413 --> 00:14:34,248
A VERY COMMON STORY.

281
00:14:34,248 --> 00:14:38,418
AND FAMILIES WOULD TAKE ACTION 

282
00:14:38,418 --> 00:14:40,020
AND THEY WOULD CREATE NOT FOR 

283
00:14:40,020 --> 00:14:43,624
PROFITS AND TRY TO GET SOMETHING

284
00:14:43,624 --> 00:14:45,559
MOVING IN THIS FIELD TO HELP 

285
00:14:45,559 --> 00:14:46,693
THEIR CHILD AND OTHERS AND 

286
00:14:46,693 --> 00:14:47,628
THAT'S WHAT WE DID.

287
00:14:47,628 --> 00:14:50,664
WE CREATED THE PROGERIA RESEARCH

288
00:14:50,664 --> 00:14:51,465
FOUNDATION.

289
00:14:51,465 --> 00:14:53,667
MY HUSBAND AND SISTER AUDREY AND

290
00:14:53,667 --> 00:14:57,704
I STARTED A FOUNDATION IN 1999 A

291
00:14:57,704 --> 00:14:59,006
FEW MONTHS AFTER SAM WAS 

292
00:14:59,006 --> 00:15:01,775
DIAGNOSED TO FIND THE CAUSE, 

293
00:15:01,775 --> 00:15:04,611
TREATMENT AND CURE FOR PROGERIA.

294
00:15:04,611 --> 00:15:06,113
AND THAT'S IT.

295
00:15:06,113 --> 00:15:14,554
VERY CLEAN, CLEAR AND FOCUSSED.

296
00:15:14,554 --> 00:15:16,323
WE HAD TO START FROM SCRATCH.

297
00:15:16,323 --> 00:15:17,658
WHAT DID WE DO?

298
00:15:17,658 --> 00:15:19,026
WE STARTED WITH PATIENTS AND 

299
00:15:19,026 --> 00:15:20,460
STARTED BY SAYING WHAT IS NEEDED

300
00:15:20,460 --> 00:15:22,162
AND NOT THERE AND WHAT WILL GET 

301
00:15:22,162 --> 00:15:23,697
SOMETHING MOVING?

302
00:15:23,697 --> 00:15:26,566
SO WE CREATED AN INTERNATIONAL 

303
00:15:26,566 --> 00:15:27,634
PROGERIA REGISTRY AND WHAT WE'RE

304
00:15:27,634 --> 00:15:30,570
ALL GOING TO TRY TO DO IS SHOW 

305
00:15:30,570 --> 00:15:32,606
YOU HOW THESE AND OTHER THINGS 

306
00:15:32,606 --> 00:15:33,740
BUILD TO SUCCESS OVER TIME.

307
00:15:33,740 --> 00:15:36,209
THE THINGS YOU DON'T HEAR ABOUT.

308
00:15:36,209 --> 00:15:38,111
THE INTERNATIONAL REGISTRY, 

309
00:15:38,111 --> 00:15:39,646
MEDICAL AND RESEARCH DATABASE TO

310
00:15:39,646 --> 00:15:45,619
UNDERSTAND THE NATURAL HISTORY 

311
00:15:45,619 --> 00:15:53,260
OF DISEASE FROM CLINICAL BANK 

312
00:15:53,260 --> 00:15:56,163
THAT SELL BLOOD AND TISSUES AND 

313
00:15:56,163 --> 00:15:57,097
BLOOD COMPONENTS TO RESEARCHERS 

314
00:15:57,097 --> 00:15:57,998
AROUND THE WORLD AND THE SEARCH 

315
00:15:57,998 --> 00:16:00,634
FOR THE GINA ASSUMING THIS WAS A

316
00:16:00,634 --> 00:16:02,436
GENETIC DISEASE OR AT LEAST WE 

317
00:16:02,436 --> 00:16:04,371
DID WHEN WE APPROACHED FRANCIS 

318
00:16:04,371 --> 00:16:05,038
WE THOUGHT IT MIGHT BE.

319
00:16:05,038 --> 00:16:09,609
WE WEREN'T SURE.

320
00:16:09,609 --> 00:16:10,911
THAT'S THE SPRING BOARD.

321
00:16:10,911 --> 00:16:11,878
THERE'S OTHER THINGS.

322
00:16:11,878 --> 00:16:14,681
THERE'S AN AMAZING CADRE OF 

323
00:16:14,681 --> 00:16:16,383
VOLUNTEERS WHO DO LOTS AND LOTS 

324
00:16:16,383 --> 00:16:18,585
OF THINGS OF COURSE.

325
00:16:18,585 --> 00:16:19,353
OUR MEDICAL RESEARCH COMMITTEE 

326
00:16:19,353 --> 00:16:21,988
AND GRANTS PROGRAM AND WORKSHOPS

327
00:16:21,988 --> 00:16:23,724
TRYING TO SAY HOW DO WE BRIDGE 

328
00:16:23,724 --> 00:16:26,360
OUR WORKSHOPS AND SCIENTIFIC 

329
00:16:26,360 --> 00:16:27,961
MEETINGS BRINGING TOGETHER THE 

330
00:16:27,961 --> 00:16:29,830
PATIENTS, CLINICIANS AND BASIC 

331
00:16:29,830 --> 00:16:30,864
SCIENTISTS AND THEY SOMETIMES 

332
00:16:30,864 --> 00:16:33,166
DON'T KNOW HOW TO TALK TO EACH 

333
00:16:33,166 --> 00:16:35,001
OTHER BUT OVER THREE DAYS EVERY 

334
00:16:35,001 --> 00:16:37,104
OTHER YEAR THEY FIND A WAY AND 

335
00:16:37,104 --> 00:16:37,738
THEN THEY COLLABORATE AND IT'S 

336
00:16:37,738 --> 00:16:45,612
BEEN WONDERFUL.

337
00:16:45,612 --> 00:16:47,647
I'M GOING TO TURN IT OVER NOW TO

338
00:16:47,647 --> 00:16:49,416
SAMMY WHO IS GOING TO TALK A 

339
00:16:49,416 --> 00:16:52,052
LITTLE BIT ABOUT HIS LIFE 

340
00:16:52,052 --> 00:16:54,087
GROWING UP AND SINCE HE HAS A 

341
00:16:54,087 --> 00:16:55,922
MEMORY LIKE I CANNOT BELIEVE, 

342
00:16:55,922 --> 00:16:57,157
EVERYTHING HE'S GOING SHARE WITH

343
00:16:57,157 --> 00:16:58,759
YOU STARTS PRETTY YOUNG AND GOES

344
00:16:58,759 --> 00:17:01,228
THROUGH TODAY.

345
00:17:01,228 --> 00:17:03,730
SAMMY, TAKE IT AWAY.

346
00:17:03,730 --> 00:17:05,198
>> THANK YOU.

347
00:17:05,198 --> 00:17:07,601
THANK YOU SO MUCH.

348
00:17:07,601 --> 00:17:15,542
I REMEMBER VERY WELL THAT MOMENT

349
00:17:15,542 --> 00:17:17,611
IN WHICH THAT PICTURE WAS SHOT 

350
00:17:17,611 --> 00:17:20,480
AND WE WERE PLAYING TOGETHER.

351
00:17:20,480 --> 00:17:25,318
IT WAS THE FIRST TIME I MET SAM 

352
00:17:25,318 --> 00:17:26,553
AND IT WAS INCREDIBLE BECAUSE IT

353
00:17:26,553 --> 00:17:32,159
WAS THE FIRST TIME I WENT TO THE

354
00:17:32,159 --> 00:17:35,295
UNITED STATES AS WELL.

355
00:17:35,295 --> 00:17:36,863
THE FIRST TIME I WENT OUT OF MY 

356
00:17:36,863 --> 00:17:38,799
COUNTRY, ITALY AND SAW OTHER 

357
00:17:38,799 --> 00:17:40,634
CHILDREN WITH PROGERIA.

358
00:17:40,634 --> 00:17:51,144
IT WAS AMAZING BECAUSE AND WE 

359
00:17:54,748 --> 00:17:56,650
WERE WEARING THE SAME THING OF 

360
00:17:56,650 --> 00:18:06,793
COURSE.

361
00:18:22,776 --> 00:18:27,614
OUR GREATEST GOAL WAS JUST TO 

362
00:18:27,614 --> 00:18:31,551
HAVE FUN TOGETHER.

363
00:18:31,551 --> 00:18:33,353
>> ONE MOMENT, SAMMY.

364
00:18:33,353 --> 00:18:35,489
WE'LL HAVE TO SHOW THIS BUT JUST

365
00:18:35,489 --> 00:18:36,990
TELL ME WHEN TO MOVE FORWARD.

366
00:18:36,990 --> 00:18:40,594
>> YEAH, IT IS OKAY.

367
00:18:40,594 --> 00:18:42,262
YOU GUYS PLAYED WITH THAT BALL 

368
00:18:42,262 --> 00:18:52,706
FOR I DON'T KNOW HOW LONG.

369
00:18:57,744 --> 00:18:59,279
IT WAS BEAUTIFUL TO STAY 

370
00:18:59,279 --> 00:19:04,551
TOGETHER BECAUSE AS YOU CAN SEE 

371
00:19:04,551 --> 00:19:12,559
THE FUN WITH SAM AND I WERE 

372
00:19:12,559 --> 00:19:14,461
STUPID GUYS SOMETIMES OF COURSE 

373
00:19:14,461 --> 00:19:16,663
BUT IT WAS BEAUTIFUL BECAUSE 

374
00:19:16,663 --> 00:19:19,699
THERE WAS THIS SENSE OF 

375
00:19:19,699 --> 00:19:21,334
COMMUNITY AND THE FIRST TIME I 

376
00:19:21,334 --> 00:19:23,737
SAW OTHER PEOPLE WITH PROGERIA 

377
00:19:23,737 --> 00:19:27,607
WAS THE FIRST TIME FOR MY 

378
00:19:27,607 --> 00:19:28,675
PARENTS AS WELL.

379
00:19:28,675 --> 00:19:30,844
NOTHING WAS REALLY KNOWN ABOUT 

380
00:19:30,844 --> 00:19:40,620
PROGERIA SO IT WAS BEAUTIFUL TO 

381
00:19:42,756 --> 00:19:44,591
MEET EACH OTHER AND EXCHANGE 

382
00:19:44,591 --> 00:19:47,627
INFORMATION AND ADVICES AND FOR 

383
00:19:47,627 --> 00:19:51,831
US, LITTLE CHILDREN, WE SAW 

384
00:19:51,831 --> 00:19:53,033
THERE WERE OTHER PEOPLE LIKE US.

385
00:19:53,033 --> 00:20:03,376
IT WAS VERY AMAZING.

386
00:20:05,645 --> 00:20:08,081
YOU CAN SEE HERE IN THIS 

387
00:20:08,081 --> 00:20:09,983
COMMUNITY FEELING HERE IS LESLIE

388
00:20:09,983 --> 00:20:13,486
AND SCOTT WERE IN FLORENCE IN 

389
00:20:13,486 --> 00:20:16,623
ITALY WITH MY PARENTS AND I.

390
00:20:16,623 --> 00:20:18,458
THEY CAME FOR VACATION AND WE 

391
00:20:18,458 --> 00:20:21,127
MET TOGETHER AND IT WAS AMAZING 

392
00:20:21,127 --> 00:20:23,697
BECAUSE THIS IS EXACTLY WHAT THE

393
00:20:23,697 --> 00:20:25,532
PROGERIA COMMUNITY IS ABOUT.

394
00:20:25,532 --> 00:20:30,236
IT'S NOT JUST TO STAY TOGETHER 

395
00:20:30,236 --> 00:20:31,705
BECAUSE WE NEED IT BUT TO STAY 

396
00:20:31,705 --> 00:20:36,710
TOGETHER BECAUSE WE WANT IT.

397
00:20:36,710 --> 00:20:39,212
WITH LESLIE AND SCOTT AND SAM OF

398
00:20:39,212 --> 00:20:44,684
COURSE, A GREAT FRIENDSHIP WERE 

399
00:20:44,684 --> 00:20:50,790
BORN AND WE HAD SO IN OCCASION 

400
00:20:50,790 --> 00:20:56,229
TO COLLABORATE AND THE NEED TO 

401
00:20:56,229 --> 00:21:00,000
SPEND QUALITY TIME TOGETHER AND 

402
00:21:00,000 --> 00:21:02,235
WE WERE IN ITALY SO IF WE DRINK 

403
00:21:02,235 --> 00:21:07,607
BEFORE 21 YEARS OLD IT WAS 

404
00:21:07,607 --> 00:21:10,844
BECAUSE IT IS LEGAL.

405
00:21:10,844 --> 00:21:21,187
OKAY, VERY BAD JOKE.

406
00:21:23,623 --> 00:21:28,695
SO FRIENDSHIP IS ABSOLUTELY 

407
00:21:28,695 --> 00:21:30,764
IMPORTANT FOR EVERY ONE WITH 

408
00:21:30,764 --> 00:21:31,031
PROGERIA.

409
00:21:31,031 --> 00:21:34,901
SO IT WAS BEAUTIFUL TO MEET 

410
00:21:34,901 --> 00:21:36,503
TOGETHER WITH OTHER PEOPLE AND 

411
00:21:36,503 --> 00:21:38,338
CHILDREN WITH PROGERIA.

412
00:21:38,338 --> 00:21:41,307
IT'S BEAUTIFUL FOR THE PATIENTS 

413
00:21:41,307 --> 00:21:46,513
THROUGHOUT THEIR OWN COMMUNITY 

414
00:21:46,513 --> 00:21:50,450
AT HOME SO HERE FOR EXAMPLE YOU 

415
00:21:50,450 --> 00:21:52,719
CAN SEE MY FRIENDS AND I HAVING 

416
00:21:52,719 --> 00:21:55,655
FUN.

417
00:21:55,655 --> 00:21:57,590
I HAD THE OPPORTUNITY TO RUN AND

418
00:21:57,590 --> 00:21:58,625
IT WAS AMAZING.

419
00:21:58,625 --> 00:22:04,230
IT WAS A BEAUTIFUL TRIP AND HERE

420
00:22:04,230 --> 00:22:06,232
YOU CAN SEE MY FRIEND AND A RUN 

421
00:22:06,232 --> 00:22:07,801
THE MARATHON TOGETHER BECAUSE TO

422
00:22:07,801 --> 00:22:11,171
RUN AND WALK IS SOMETHING I 

423
00:22:11,171 --> 00:22:16,676
CAN'T DO.

424
00:22:16,676 --> 00:22:19,979
I CAN'T WALK FOR SO LONG OR RUN 

425
00:22:19,979 --> 00:22:20,580
AT ALL.

426
00:22:20,580 --> 00:22:21,581
TO RUN IS THE THING YOU CAN'T 

427
00:22:21,581 --> 00:22:28,655
DO, WE WILL DO IT.

428
00:22:28,655 --> 00:22:30,623
AND FRIENDS ARE BEAUTIFUL FOR 

429
00:22:30,623 --> 00:22:30,790
ME.

430
00:22:30,790 --> 00:22:34,627
THEY'RE ONE OF THE REASONS I 

431
00:22:34,627 --> 00:22:39,599
WAKE UP EVERY MORNING WITH A 

432
00:22:39,599 --> 00:22:42,402
SMILE THEY ARE LIKE A FAMILY FOR

433
00:22:42,402 --> 00:22:43,036
ME AND I COULDN'T STAY WITHOUT 

434
00:22:43,036 --> 00:22:52,512
THEM.

435
00:22:52,512 --> 00:22:58,318
SO AS LESLIE WAS TELLING BEFORE,

436
00:22:58,318 --> 00:23:00,353
THE NONPROFITS ARE EXTREMELY 

437
00:23:00,353 --> 00:23:01,354
IMPORTANT FOR ANY RARE DISEASE.

438
00:23:01,354 --> 00:23:07,327
AS A FAMILY, WE WERE VERY LUCKY 

439
00:23:07,327 --> 00:23:09,662
BECAUSE WHEN MY PARENTS AND I 

440
00:23:09,662 --> 00:23:11,030
WENT FOR THE FIRST TIME FOR 

441
00:23:11,030 --> 00:23:15,502
MEETING THE OTHER KIDS THE 

442
00:23:15,502 --> 00:23:20,673
PROGERIA FOUNDATION WAS FUNDED 

443
00:23:20,673 --> 00:23:23,143
ONE YEAR BEFORE SO WE HAD 

444
00:23:23,143 --> 00:23:25,111
SOMEONE WORKING FOR US, SOMEONE 

445
00:23:25,111 --> 00:23:30,617
WORKING FOR MY LIFE, FOR GIVING 

446
00:23:30,617 --> 00:23:32,085
ME A BETTER QUALITY OF LIFE AND 

447
00:23:32,085 --> 00:23:34,988
BETTER LIFE EXPECTANCY.

448
00:23:34,988 --> 00:23:39,626
IT WAS GREAT TO KNOW THIS 

449
00:23:39,626 --> 00:23:41,094
BECAUSE WE WERE NOT ALONE.

450
00:23:41,094 --> 00:23:42,362
WHEN I WAS 10 YEARS OLD I 

451
00:23:42,362 --> 00:23:44,664
DECIDED IT WAS TIME FOR ME AND 

452
00:23:44,664 --> 00:23:52,472
FOR US AS A FAMILY TO DO 

453
00:23:52,472 --> 00:23:53,973
SOMETHING AND ASKING MY PARENTS 

454
00:23:53,973 --> 00:23:55,141
WHY IN THE TELEVISION PEOPLE ARE

455
00:23:55,141 --> 00:23:56,743
TALKING ABOUT SO MANY DIFFERENT 

456
00:23:56,743 --> 00:24:01,314
DISEASES BUT NOT ABOUT PROGERIA 

457
00:24:01,314 --> 00:24:09,656
AND THEY TOLD ME PROGERIA IS TOO

458
00:24:09,656 --> 00:24:09,889
RARE.

459
00:24:09,889 --> 00:24:11,891
WE SHOULD FOUND A FOUNDATION FOR

460
00:24:11,891 --> 00:24:13,126
PROGERIA AND I TOLD THEM, OKAY, 

461
00:24:13,126 --> 00:24:20,533
LET'S DO THAT AND WE DID IT.

462
00:24:20,533 --> 00:24:22,836
IT WAS A GREAT CHANGE IN MY 

463
00:24:22,836 --> 00:24:23,036
LIFE.

464
00:24:23,036 --> 00:24:24,671
MY PRIVATE LIFE IS ALMOST GONE 

465
00:24:24,671 --> 00:24:29,642
NOW BECAUSE MY FOUNDATION IS 

466
00:24:29,642 --> 00:24:32,679
VERY ACTIVE.

467
00:24:32,679 --> 00:24:40,220
WE'RE DOING SO MANY DISCLOSURE 

468
00:24:40,220 --> 00:24:41,187
EVENTS AND IMPORTANT THE 

469
00:24:41,187 --> 00:24:43,223
COLLABORATION WITH THE PROGERIA 

470
00:24:43,223 --> 00:24:51,631
FOUNDATION BECAUSE IT HAD A 

471
00:24:51,631 --> 00:24:52,966
STRUCTURE WE DIDN'T NEED TO 

472
00:24:52,966 --> 00:24:56,402
INVENT ANYTHING JUST SAY TO 

473
00:24:56,402 --> 00:24:57,370
OURSELVES, OKAY, IT'S TIME TO DO

474
00:24:57,370 --> 00:25:03,543
WHAT THEY ARE DOING.

475
00:25:03,543 --> 00:25:04,644
-- 

476
00:25:04,644 --> 00:25:06,079
>> I'M CURIOUS, WHAT ARE
YOU 

477
00:25:06,079 --> 00:25:07,347
DOING RIGHT IN THE LOWER RIGHT 

478
00:25:07,347 --> 00:25:09,215
OF THIS PICTURE AND THERE'S A 

479
00:25:09,215 --> 00:25:10,717
MASSIVE NUMBER OF PEOPLE AND 

480
00:25:10,717 --> 00:25:11,751
YOU'RE STANDING ON THE STAGE 

481
00:25:11,751 --> 00:25:14,587
TAKING A SELFIE WITH YOU AND 

482
00:25:14,587 --> 00:25:15,588
THEM IN THE BACKGROUND.

483
00:25:15,588 --> 00:25:17,090
WHAT IS GOING ON?

484
00:25:17,090 --> 00:25:20,426
>> I WAS IN PADUA AND
THERE WERE

485
00:25:20,426 --> 00:25:23,296
LIKE 100,000 YOUNG PEOPLE THERE.

486
00:25:23,296 --> 00:25:28,301
IT WAS CRAZY.

487
00:25:28,301 --> 00:25:32,739
IT WAS FOR SUSTAINING PEACE IN 

488
00:25:32,739 --> 00:25:36,509
GENERAL AND ASKED ME TO TALK 

489
00:25:36,509 --> 00:25:39,012
ABOUT MY LIFE AND ABOUT RESEARCH

490
00:25:39,012 --> 00:25:40,546
BECAUSE RESEARCH IS IMPORTANT 

491
00:25:40,546 --> 00:25:45,051
FOR PEACE TOO BECAUSE IT'S 

492
00:25:45,051 --> 00:25:45,919
INTERNATIONAL AND A BEAUTIFUL 

493
00:25:45,919 --> 00:25:47,353
PLATFORM TO MAKE ALL THE PEOPLE 

494
00:25:47,353 --> 00:25:51,524
THE SAME, NO DIFFERENCES OR AT 

495
00:25:51,524 --> 00:25:53,226
LEAST WITH DIFFERENCES BUT 

496
00:25:53,226 --> 00:25:54,694
COLLABORATING ONE ANOTHER AND IT

497
00:25:54,694 --> 00:26:03,336
WAS ABSOLUTELY CRAZY BECAUSE TO 

498
00:26:03,336 --> 00:26:04,771
SEE ALL THOSE PEOPLE IN FRONT OF

499
00:26:04,771 --> 00:26:07,607
ME WAS SCARY AND FUNNY AT THE 

500
00:26:07,607 --> 00:26:13,613
SAME TIME.

501
00:26:13,613 --> 00:26:16,182
IT WAS AMAZING.

502
00:26:16,182 --> 00:26:19,585
THE BEAUTIFUL THING IS THAT I 

503
00:26:19,585 --> 00:26:23,156
CAN SEE SO MANY PEOPLE 

504
00:26:23,156 --> 00:26:26,626
INTERESTED IN WHAT WE'RE DOING.

505
00:26:26,626 --> 00:26:27,994
THERE'S A HUNGER FOR RESEARCH.

506
00:26:27,994 --> 00:26:32,832
THEY WANT TO KNOW WHAT WE ARE 

507
00:26:32,832 --> 00:26:35,368
DOING AND IT IS GREAT BECAUSE 

508
00:26:35,368 --> 00:26:41,541
THE OVERWHELMING MAJORITY OF THE

509
00:26:41,541 --> 00:26:43,109
PEOPLE DON'T KNOW ABOUT PROGERIA

510
00:26:43,109 --> 00:26:47,680
OR HAVE NEVER SEEN A PERSON WITH

511
00:26:47,680 --> 00:26:48,681
PROGERIA BUT THEY ARE INTERESTED

512
00:26:48,681 --> 00:26:49,282
IN SUSTAINING US AND THAT'S 

513
00:26:49,282 --> 00:26:58,858
GREAT.

514
00:26:58,858 --> 00:27:05,565
THIS IS MY BEST PORTRAIT.

515
00:27:05,565 --> 00:27:10,336
I WAS IN ROSWELL AND IT WAS 

516
00:27:10,336 --> 00:27:12,739
FUNNY BECAUSE THEY'RE KNOWN FOR 

517
00:27:12,739 --> 00:27:18,511
THE CRASH IN 1947.

518
00:27:18,511 --> 00:27:20,446
USUALLY BABIES TELL ME YOU LOOK 

519
00:27:20,446 --> 00:27:21,314
LIKE AN ALIEN.

520
00:27:21,314 --> 00:27:23,182
SO I GOT MY REVENGE ON THE 

521
00:27:23,182 --> 00:27:27,520
WORLD.

522
00:27:27,520 --> 00:27:30,223
I PLAYED THE ALIEN PART IN 

523
00:27:30,223 --> 00:27:32,325
ROSWELL AND IT WAS AMAZING TO 

524
00:27:32,325 --> 00:27:33,526
SEE THE FACES OF THIS PEOPLE 

525
00:27:33,526 --> 00:27:37,196
THERE LOOKING AT ME AND SAYING, 

526
00:27:37,196 --> 00:27:37,597
WHAT IS GOING ON.

527
00:27:37,597 --> 00:27:41,667
IT'S REAL.

528
00:27:41,667 --> 00:27:44,670
I REALLY EXIST.

529
00:27:44,670 --> 00:27:48,307
SO YEAH, I'M DEFINITELY A STUPID

530
00:27:48,307 --> 00:27:49,575
GUY.

531
00:27:49,575 --> 00:27:51,144
IT WAS BEAUTIFUL TO JOKE INSIDE 

532
00:27:51,144 --> 00:27:59,552
THE MUSEUM.

533
00:27:59,552 --> 00:28:01,487
SO IF PROGER YA DOES NOT AVOID 

534
00:28:01,487 --> 00:28:07,527
ANYONE TO HAVE A HAPPY LIFE AND 

535
00:28:07,527 --> 00:28:08,895
TO ENJOY LIFE, PROGERIA IS A 

536
00:28:08,895 --> 00:28:11,397
DISEASE SO IT'S SOMETHING WE 

537
00:28:11,397 --> 00:28:12,999
HAVE TO FIGHT.

538
00:28:12,999 --> 00:28:15,601
AND TO LIVE WITH PROGERIA IS NOT

539
00:28:15,601 --> 00:28:18,604
SIMPLE.

540
00:28:18,604 --> 00:28:24,444
THERE'S NOT ONLY A RARE DISEASE 

541
00:28:24,444 --> 00:28:25,144
IT'S A VERY CRITICAL AND 

542
00:28:25,144 --> 00:28:30,917
DIFFICULT DISEASE TO WORK WITH.

543
00:28:30,917 --> 00:28:32,585
PROGERIA IS SOMETIMES PAINFUL.

544
00:28:32,585 --> 00:28:37,023
YOU HAVE PROBLEMS IN THE BONES 

545
00:28:37,023 --> 00:28:38,591
YOU HAVE PAIN EVERYWHERE YOU 

546
00:28:38,591 --> 00:28:40,059
HAVE PAIN IN THE FOOT, YOU CAN'T

547
00:28:40,059 --> 00:28:46,666
WALK A LOT AND DISLOCATIONS OF 

548
00:28:46,666 --> 00:28:49,535
THE HIPS SO YOU HAVE TO STAY IN 

549
00:28:49,535 --> 00:28:56,008
THE BED FOR A LONG TIME UNTIL 

550
00:28:56,008 --> 00:29:01,013
YOU GET BETTER AND IT IS VERY 

551
00:29:01,013 --> 00:29:02,181
DIFFICULT BECAUSE IT IS PAINFUL.

552
00:29:02,181 --> 00:29:04,684
IT'S NOT EASY TO MANAGE.

553
00:29:04,684 --> 00:29:10,189
IN ANY CASE, PROGERIA BECAUSE OF

554
00:29:10,189 --> 00:29:13,326
ALL THESE PROBLEMS AVOID YOU TO 

555
00:29:13,326 --> 00:29:17,563
BE AUTONOMOUS OR INDEPENDENT AT 

556
00:29:17,563 --> 00:29:19,465
WHATEVER PERCENT.

557
00:29:19,465 --> 00:29:21,167
IN ANY CASE TOGETHER WITH THE 

558
00:29:21,167 --> 00:29:26,539
PAIN THERE'S THE CONSCIOUSNESS 

559
00:29:26,539 --> 00:29:31,310
YOU'RE IN THE WORLD NOT BUILT 

560
00:29:31,310 --> 00:29:36,449
FOR YOU BECAUSE EVERYTHING -- 

561
00:29:36,449 --> 00:29:40,052
HERE YOU CAN SEE WHEN I HAD MY 

562
00:29:40,052 --> 00:29:44,056
SURGERY, IT WAS A DIFFICULT 

563
00:29:44,056 --> 00:29:45,391
MOMENT IN MY LIFE.

564
00:29:45,391 --> 00:29:49,462
THE RISK WAS HIGH, 50/50.

565
00:29:49,462 --> 00:29:53,599
50% IT WAS OKAY, 50% I WASN'T 

566
00:29:53,599 --> 00:29:55,902
ABLE TO SURVIVE.

567
00:29:55,902 --> 00:29:58,004
IT WAS VERY DIFFICULT TO MAKE A 

568
00:29:58,004 --> 00:30:04,577
CHOICE BUT I HAD NO OTHER OPTION

569
00:30:04,577 --> 00:30:05,211
HAVE THE SURGERY OR WAIT UNTIL 

570
00:30:05,211 --> 00:30:09,315
IT WAS TOO LATE.

571
00:30:09,315 --> 00:30:14,654
THIS IS WHAT PROGERIA IS.

572
00:30:14,654 --> 00:30:18,558
TOO MANY TIMES I HAD TO SAY 

573
00:30:18,558 --> 00:30:20,793
GOOD-BYE TO OTHER PATIENTS AND 

574
00:30:20,793 --> 00:30:22,094
IT IS NOT JUST TO SAY GOOD-BYE 

575
00:30:22,094 --> 00:30:22,828
TO A PATIENT.

576
00:30:22,828 --> 00:30:25,531
IT IS ABOUT TO SAY GOOD-BYE TO A

577
00:30:25,531 --> 00:30:27,166
FRIEND.

578
00:30:27,166 --> 00:30:29,702
AND IT IS VERY VERY DIFFICULT 

579
00:30:29,702 --> 00:30:32,638
BECAUSE THEY ARE FRIENDS AND 

580
00:30:32,638 --> 00:30:38,611
SURELY YOU SAY IT COULD BE ME.

581
00:30:38,611 --> 00:30:43,349
WHY AM I HERE AND THEY ARE NOT.

582
00:30:43,349 --> 00:30:53,893
THIS IS WHAT PROGERIA IS ABOUT.

583
00:30:59,765 --> 00:31:03,202
PROGERIA LED ME TO DISCUSS 

584
00:31:03,202 --> 00:31:09,308
SCIENCE IS MY FRIEND AND IT WAS 

585
00:31:09,308 --> 00:31:11,277
A VERY SCIENTIFIC END AND I 

586
00:31:11,277 --> 00:31:20,820
DECIDED TO BE A SCIENTIST FOR 

587
00:31:20,820 --> 00:31:23,356
STUDYING PROGERIA BUT I DECIDED 

588
00:31:23,356 --> 00:31:31,063
TO BE A SCIENTIST BECAUSE I SAW 

589
00:31:31,063 --> 00:31:32,665
THE DRAW IN SCIENCE SINCE I WAS 

590
00:31:32,665 --> 00:31:33,299
VERY YOUNG.

591
00:31:33,299 --> 00:31:36,602
I WAS LOOKING AT LESLIE AND HER 

592
00:31:36,602 --> 00:31:40,406
TEAM WORKING VERY VERY HARD FOR 

593
00:31:40,406 --> 00:31:42,475
HELPING ME AND I THOUGHT OKAY, I

594
00:31:42,475 --> 00:31:46,879
WANT TO BE THAT KIND OF PERSON 

595
00:31:46,879 --> 00:31:48,314
BECAUSE I WANT TO HELP PEOPLE 

596
00:31:48,314 --> 00:31:51,584
AND MAYBE THERE'S NOT ANOTHER 

597
00:31:51,584 --> 00:31:57,556
WAY FOR ME TO BE HELPFUL TO 

598
00:31:57,556 --> 00:31:59,525
PEOPLE.

599
00:31:59,525 --> 00:32:01,027
NOW, CAN I SAY WE'RE COLLEAGUES?

600
00:32:01,027 --> 00:32:02,328
>> YES, WE CAN.

601
00:32:02,328 --> 00:32:04,463
>> AND I'M SO PROUD.

602
00:32:04,463 --> 00:32:06,065
>> WE'RE SO PROUD TO BE 

603
00:32:06,065 --> 00:32:07,333
COLLEAGUES OF YOURS TOO.

604
00:32:07,333 --> 00:32:08,901
THANK YOU, SAMMY.

605
00:32:08,901 --> 00:32:10,002
I THINK WE HAVE TIME FOR ONE 

606
00:32:10,002 --> 00:32:11,404
QUESTION FROM THE WEB.

607
00:32:11,404 --> 00:32:12,605
IS THERE SOMEBODY THAT TYPED IN 

608
00:32:12,605 --> 00:32:15,608
A QUESTION WE MIGHT WANT TO 

609
00:32:15,608 --> 00:32:25,751
ANSWER?

610
00:32:26,719 --> 00:32:28,888
I'D LIKE TO ASK SOMETHING.

611
00:32:28,888 --> 00:32:32,058
SAMMY, WHEN I FIRST MEET 

612
00:32:32,058 --> 00:32:33,492
FAMILIES WHEN THEY'RE NEWLY 

613
00:32:33,492 --> 00:32:39,632
DIAGNOSED OR COME TO ME WITH 

614
00:32:39,632 --> 00:32:50,176
DIAGNOSTICS, ABOUT WHAT ADVISE 

615
00:32:51,377 --> 00:32:52,478
TO YOU GIVE THE FIRST TIME?

616
00:32:52,478 --> 00:32:59,118
>> THIS IS A VERY GOOD
QUESTION.

617
00:32:59,118 --> 00:33:01,987
IT'S DIFFICULT TO GIVE SOMEONE 

618
00:33:01,987 --> 00:33:03,356
ADVICE BECAUSE EVERYONE IS 

619
00:33:03,356 --> 00:33:03,622
DIFFERENT.

620
00:33:03,622 --> 00:33:04,256
EVERYONE TAKES IT IN DIFFERENT 

621
00:33:04,256 --> 00:33:08,427
WAY.

622
00:33:08,427 --> 00:33:11,597
CERTAINLY THE FIRST THING WE SAY

623
00:33:11,597 --> 00:33:18,104
NOW IS OKAY.

624
00:33:18,104 --> 00:33:19,538
THERE IS AN INTERNATIONAL TEAM 

625
00:33:19,538 --> 00:33:23,709
WORKING FOR YOUR SOUL OR FOR 

626
00:33:23,709 --> 00:33:23,876
YOU.

627
00:33:23,876 --> 00:33:24,710
IT'S DIFFICULT.

628
00:33:24,710 --> 00:33:29,181
NOBODY IS HIDING IT BUT THERE IS

629
00:33:29,181 --> 00:33:31,450
A HOPE THERE'S A POSSIBILITY TO 

630
00:33:31,450 --> 00:33:32,585
STAY BETTER.

631
00:33:32,585 --> 00:33:35,588
THERE'S A POSSIBILITY TO MANAGE 

632
00:33:35,588 --> 00:33:37,656
PROGERIA BETTER THAN IN THE 

633
00:33:37,656 --> 00:33:37,857
PAST.

634
00:33:37,857 --> 00:33:40,292
THIS IS THE FIRST THING WE SAY 

635
00:33:40,292 --> 00:33:41,560
AND THE OTHER THING IS YOUR SON,

636
00:33:41,560 --> 00:33:48,200
YOUR DAUGHTER, HAS A DISEASE, 

637
00:33:48,200 --> 00:33:48,567
OKAY.

638
00:33:48,567 --> 00:33:51,637
BUT FIRSTLY, THEY ARE A PERSON 

639
00:33:51,637 --> 00:33:58,277
AND HE OR SHE HAS TO DEVELOP AS 

640
00:33:58,277 --> 00:34:03,315
NORMAL AS POSSIBLE AND HE CAN DO

641
00:34:03,315 --> 00:34:09,255
A LOT IN HIS LIFE SO PROGERIA 

642
00:34:09,255 --> 00:34:12,024
DOES NOT AVOID TO BE -- TO BE A 

643
00:34:12,024 --> 00:34:13,426
PERSON -- TO BE REAL AND 

644
00:34:13,426 --> 00:34:15,594
AUTHENTIC.

645
00:34:15,594 --> 00:34:19,598
THIS IS THE FIRST THING.

646
00:34:19,598 --> 00:34:21,500
I HAVE A QUESTION FOR YOU TOO, 

647
00:34:21,500 --> 00:34:22,501
LESLIE.

648
00:34:22,501 --> 00:34:24,603
SOMETIMES EMOTION AND HUMOR -- 

649
00:34:24,603 --> 00:34:27,807
THE HUMAN PART OF A PERSON IS 

650
00:34:27,807 --> 00:34:33,479
SEEN AS OPPOSITION TO THE 

651
00:34:33,479 --> 00:34:39,652
SCIENTIFIC PART BECAUSE OF THE 

652
00:34:39,652 --> 00:34:46,091
NATIONALITY AND WHO COULD 

653
00:34:46,091 --> 00:34:49,361
EXPLAIN BETTER THIS THING 

654
00:34:49,361 --> 00:34:51,464
>> I'LL KEEP IT SHORT
BECAUSE WE

655
00:34:51,464 --> 00:34:54,533
WANT TO GET TO FRANCIS' EXCITING

656
00:34:54,533 --> 00:34:58,304
NEXT PART AND SAMMY, YOU ASKED A

657
00:34:58,304 --> 00:35:00,973
PERFECT QUESTION BECAUSE IT'S 

658
00:35:00,973 --> 00:35:03,576
THE LOVE AND THE PASSION THAT 

659
00:35:03,576 --> 00:35:10,583
DRIVES YOU TO DO THE BEST 

660
00:35:10,583 --> 00:35:11,684
SCIENCE POSSIBLE AND I THINK 

661
00:35:11,684 --> 00:35:13,919
IT'S BORN OUT WHEN YOU DO YOUR 

662
00:35:13,919 --> 00:35:14,753
SCIENCE, IT REALLY MEANS 

663
00:35:14,753 --> 00:35:15,354
SOMETHING.

664
00:35:15,354 --> 00:35:18,090
IT'S GOING TO BE TRANSLATED INTO

665
00:35:18,090 --> 00:35:18,390
SOMETHING.

666
00:35:18,390 --> 00:35:21,727
YOU HAVE A HYPOTHESIS AND THAT 

667
00:35:21,727 --> 00:35:23,195
TURNS OUT TO BE WRONG, YOU WANT 

668
00:35:23,195 --> 00:35:23,529
TO KNOW.

669
00:35:23,529 --> 00:35:25,931
YOU WANT TO SAY, OKAY, THIS WAS 

670
00:35:25,931 --> 00:35:27,032
WRONG, LET'S MOVE ON BECAUSE I 

671
00:35:27,032 --> 00:35:29,602
DON'T WANT TO GO DOWN THE WRONG 

672
00:35:29,602 --> 00:35:30,135
PATHWAY.

673
00:35:30,135 --> 00:35:31,871
YOU WANT TO GO DOWN THE RIGHT 

674
00:35:31,871 --> 00:35:33,172
PATHWAY SO YOU JUST PICK 

675
00:35:33,172 --> 00:35:33,806
YOURSELF UP AND START AGAIN AND 

676
00:35:33,806 --> 00:35:39,645
START SOMETHING NEW.

677
00:35:39,645 --> 00:35:42,014
SO THE PASSION IS THERE FOR 

678
00:35:42,014 --> 00:35:44,583
FAMILY MEMBERS LIKE ME AND 

679
00:35:44,583 --> 00:35:47,119
SCIENTISTS AND CLINICIANS AND 

680
00:35:47,119 --> 00:35:48,187
THERE ARE FOR US ALL.

681
00:35:48,187 --> 00:35:54,493
IT'S THE BEST PART AND NOT A 

682
00:35:54,493 --> 00:35:55,528
DISADVANTAGE.

683
00:35:55,528 --> 00:35:57,730
THAT'S A PERFECT TRANSITION TO 

684
00:35:57,730 --> 00:35:59,598
OUR PASSIONATE SCIENTISTS.

685
00:35:59,598 --> 00:36:01,200
FRANCIS, CAN YOU TELL US ABOUT 

686
00:36:01,200 --> 00:36:11,443
YOUR JOURNEY?

687
00:36:12,678 --> 00:36:14,947
>> WE'LL HEAR MORE FROM
SAMMY 

688
00:36:14,947 --> 00:36:17,583
AND TO BE PART OF THIS WITH 

689
00:36:17,583 --> 00:36:19,518
LESLIE MY FRIEND NOW OVER 20 

690
00:36:19,518 --> 00:36:21,253
YEARS AS WE TOGETHER TRY TO 

691
00:36:21,253 --> 00:36:24,523
FIGURE OUT WHAT TO DO ABOUT THIS

692
00:36:24,523 --> 00:36:28,160
TERRIBLY RARE BUT POIGNANT 

693
00:36:28,160 --> 00:36:29,695
DISORDER CALLING OUT FOR 

694
00:36:29,695 --> 00:36:31,730
SOMEBODY TO FIGURE IT OUT.

695
00:36:31,730 --> 00:36:38,704
I FIRST MET LESLIE AND SON SAM 

696
00:36:38,704 --> 00:36:45,010
23 YEARS AGO.

697
00:36:45,010 --> 00:36:48,614
THIS WAS SHORTLY AFTER THEY 

698
00:36:48,614 --> 00:36:49,848
STARTED PROGERIA SEARCH 

699
00:36:49,848 --> 00:36:51,550
FOUNDATION AND HOW DO WE GET 

700
00:36:51,550 --> 00:36:55,387
SOMEBODY TO WORK ON ?

701
00:36:55,387 --> 00:36:57,957
WE HAD A GOOD TIME WORKING ON 

702
00:36:57,957 --> 00:37:01,293
THIS AND LESLIE AND SCOTT WERE 

703
00:37:01,293 --> 00:37:01,961
COMPELLING PEOPLE.

704
00:37:01,961 --> 00:37:04,363
I SAID, SURE, I'LL TRY TO HELP A

705
00:37:04,363 --> 00:37:06,065
LITTLE BIT AND TRY TO IDENTIFIED

706
00:37:06,065 --> 00:37:08,000
SCIENTISTS WHO MAY WANT TO 

707
00:37:08,000 --> 00:37:09,368
POTENTIALLY WORK ON THIS RARE 

708
00:37:09,368 --> 00:37:09,602
DISEASE.

709
00:37:09,602 --> 00:37:11,136
MAYBE I CAN HELP SET UP AN IDEA 

710
00:37:11,136 --> 00:37:16,375
FOR A WORKSHOP AND I GOT HOOKED.

711
00:37:16,375 --> 00:37:19,211
IT WAS A POSTDOC IN MY LAB WHO 

712
00:37:19,211 --> 00:37:20,913
DECIDED SHE WAS GOING TO TRY TO 

713
00:37:20,913 --> 00:37:22,014
FIND THE GENE BECAUSE IT JUST 

714
00:37:22,014 --> 00:37:23,148
SEEMED LIKE SOMETHING THAT 

715
00:37:23,148 --> 00:37:27,586
NEEDED TO HAPPEN.

716
00:37:27,586 --> 00:37:30,222
MEANWHILE ALONG THE WAY I GOT TO

717
00:37:30,222 --> 00:37:32,625
SPEND TIME WITH LESLIE AND SCOTT

718
00:37:32,625 --> 00:37:34,460
AND SAM AND PLAYING MUSIC WITH A

719
00:37:34,460 --> 00:37:35,995
GOOD DRUMMER, SAM WAS.

720
00:37:35,995 --> 00:37:37,630
AND THEN ON DOWN THROUGH THE 

721
00:37:37,630 --> 00:37:39,598
YEARS I WOULD SAY SAM AND I 

722
00:37:39,598 --> 00:37:40,933
BECAME REALLY GOOD FRIENDS.

723
00:37:40,933 --> 00:37:46,705
HERE'S A MUCH LATER PICTURE IN 

724
00:37:46,705 --> 00:37:47,606
THE CIRCUMSTANCE OF A 

725
00:37:47,606 --> 00:37:48,807
PRESENTATION THAT INVOLVED 

726
00:37:48,807 --> 00:37:50,109
COOKIE MONSTER AND OF COURSE 

727
00:37:50,109 --> 00:37:54,313
NEEDED A PICTURE WITH COOKIE 

728
00:37:54,313 --> 00:37:54,580
MONSTER.

729
00:37:54,580 --> 00:37:56,382
WE LOST SAM AT AGE 17.

730
00:37:56,382 --> 00:37:58,317
HE'S AN OUR HEART EVERY TIME WE 

731
00:37:58,317 --> 00:37:59,051
TALK ABOUT THIS DISEASE AND WORK

732
00:37:59,051 --> 00:38:08,260
ON THIS DISEASE.

733
00:38:08,260 --> 00:38:11,230
I'M GLAD TO HAVE HIS FRIEND 

734
00:38:11,230 --> 00:38:16,735
SAMMY, HERE AS AN AMAZING 

735
00:38:16,735 --> 00:38:17,169
CONTRIBUTOR.

736
00:38:17,169 --> 00:38:20,639
AND I GOT A CALL SAYING I THINK 

737
00:38:20,639 --> 00:38:22,908
WE HAVE SOMETHING IT LOOKS LIKE 

738
00:38:22,908 --> 00:38:27,746
THE DNA SAMPLES WITH PROGERIA 

739
00:38:27,746 --> 00:38:32,217
SEEM TO SHARE AN UNUSUAL 

740
00:38:32,217 --> 00:38:34,753
SPELLING IN THE LAMIN A GENE AND

741
00:38:34,753 --> 00:38:37,356
LOOKS LIKE A SILENT MUTATION AND

742
00:38:37,356 --> 00:38:39,425
HOW CAN THAT BE POSSIBLY THE 

743
00:38:39,425 --> 00:38:40,092
RIGHT ANSWER.

744
00:38:40,092 --> 00:38:42,127
AS YOU CAN SEE, WE PUBLISHED A 

745
00:38:42,127 --> 00:38:43,896
PAPER AND FIGURED OUT IT WAS THE

746
00:38:43,896 --> 00:38:45,798
RIGHT ANSWER AND THESE WERE 

747
00:38:45,798 --> 00:38:47,566
RECURRENT DE NOVO POINT 

748
00:38:47,566 --> 00:38:48,067
MUTATION.

749
00:38:48,067 --> 00:38:50,069
THE WAY WE FIGURED OUT WAS THIS 

750
00:38:50,069 --> 00:38:52,705
HAD TO BE THE CAUSE WE HAD 

751
00:38:52,705 --> 00:38:54,573
SEVERAL PARENTS WHOSE KIDS WERE 

752
00:38:54,573 --> 00:38:57,209
AVAILABLE AND A C2 MUTATION IN 

753
00:38:57,209 --> 00:38:59,878
THE LAMIN A GENE AND THE PARENTS

754
00:38:59,878 --> 00:39:02,281
DIDN'T HAVE IT AND A MUTATION IN

755
00:39:02,281 --> 00:39:04,817
THE SAME NUCLEOTIDE WHAT IS 

756
00:39:04,817 --> 00:39:05,384
GOING ON HERE.

757
00:39:05,384 --> 00:39:08,721
WE LOOKED AT THE SEQUENCE AND 

758
00:39:08,721 --> 00:39:16,562
THERE YOU SEE THE C TO A T AND 

759
00:39:16,562 --> 00:39:21,734
I'M SURE YOU ALL MEMORIZED THE 

760
00:39:21,734 --> 00:39:22,968
GENETIC CODE, MAYBE NOT.

761
00:39:22,968 --> 00:39:25,437
I HAD TO LOOK IT UP AND THERE'S 

762
00:39:25,437 --> 00:39:26,872
ANOTHER POINT THE POINT MUTATION

763
00:39:26,872 --> 00:39:28,507
CAUSES TROUBLE FOR THIS 

764
00:39:28,507 --> 00:39:30,676
PARTICULAR GENE AND THAT'S 

765
00:39:30,676 --> 00:39:34,313
BECAUSE IT ACTUALLY CREATES OR 

766
00:39:34,313 --> 00:39:37,549
ACTIVATES, I SHOULD SAY, A 

767
00:39:37,549 --> 00:39:39,084
CRYPTIC SPLICE SITE DONOR IN THE

768
00:39:39,084 --> 00:39:42,721
MIDDLE OF AXON 11 USED A LITTLE 

769
00:39:42,721 --> 00:39:45,657
BIT BY ALL OF YOU BUT IN A LOW 

770
00:39:45,657 --> 00:39:48,193
LEVEL EXCEPT MAKE WHEN YOU'RE 

771
00:39:48,193 --> 00:39:51,597
CELLS ARE REALLY HEADING FOR 

772
00:39:51,597 --> 00:39:53,832
SENESCENCE IN WHICH IT TURNS ON 

773
00:39:53,832 --> 00:39:54,032
A BIT.

774
00:39:54,032 --> 00:39:56,535
IN THESE KIDS THAT ONE LETTER 

775
00:39:56,535 --> 00:40:00,172
CHANGE MAKES THE SEQUENCE IN 

776
00:40:00,172 --> 00:40:02,274
AXON 11 BETTER TO THE SPLICE 

777
00:40:02,274 --> 00:40:03,509
DONOR CONSENSUS.

778
00:40:03,509 --> 00:40:05,043
WE POSTULATED PROBABLY THE SAME 

779
00:40:05,043 --> 00:40:06,545
DAY OR AT LEAST THAT WEEKEND 

780
00:40:06,545 --> 00:40:09,782
THAT MIGHT BE THE MECHANISM AND 

781
00:40:09,782 --> 00:40:11,150
YOU'RE ACTIVATING THEREFORE A 

782
00:40:11,150 --> 00:40:13,452
SPLICE THAT BASICALLY SKIPS OVER

783
00:40:13,452 --> 00:40:16,021
THE LAST PART OF AXON 11.

784
00:40:16,021 --> 00:40:19,191
ALL OF YOU MOLECULAR BIOLOGISTS 

785
00:40:19,191 --> 00:40:21,293
ASKING IF THAT'S A MULTIPLE WITH

786
00:40:21,293 --> 00:40:24,363
THREE NUCLEOTIDES, YES.

787
00:40:24,363 --> 00:40:26,632
150 NUCLEOTIDES THAT GETS 

788
00:40:26,632 --> 00:40:26,865
SKIPPED.

789
00:40:26,865 --> 00:40:28,267
WHAT'S THAT MEAN WHEN YOU MAKE 

790
00:40:28,267 --> 00:40:29,034
THE PROTEIN?

791
00:40:29,034 --> 00:40:34,673
YOU'LL MAKE A LAMIN A PROTEIN 

792
00:40:34,673 --> 00:40:37,576
MISSING 15 ACIDS AND YOU HAVE 

793
00:40:37,576 --> 00:40:39,578
STILL HAVE AXON 12 AND WE CALL 

794
00:40:39,578 --> 00:40:42,314
THAT PROGERIA.

795
00:40:42,314 --> 00:40:49,054
THAT PROTEIN.

796
00:40:49,054 --> 00:40:50,756
BOTTOM LINE THIS MAKES THE CELL 

797
00:40:50,756 --> 00:40:53,158
SENESCE PREMATURELY BECAUSE IT 

798
00:40:53,158 --> 00:40:55,561
REALLY MESSES UP THE NUCLEAR 

799
00:40:55,561 --> 00:40:58,363
STRUCTURE.

800
00:40:58,363 --> 00:41:00,132
SO WHY WOULD THAT CAUSE A TOXIC 

801
00:41:00,132 --> 00:41:00,399
PROTEIN?

802
00:41:00,399 --> 00:41:02,935
WE NEEDED TO DEPEND ON THE 

803
00:41:02,935 --> 00:41:05,470
WONDERFUL BASIC SCIENCE DONE BY 

804
00:41:05,470 --> 00:41:07,806
PEOPLE STUDYING LAMIN A AND JUST

805
00:41:07,806 --> 00:41:10,209
STOOD ON THEIR SHOULDERS AND SEE

806
00:41:10,209 --> 00:41:12,811
IMMEDIATELY WHY THIS COULD BE A 

807
00:41:12,811 --> 00:41:14,246
PROBLEM NORMALLY LAMIN A HAS 

808
00:41:14,246 --> 00:41:16,348
POST TRANSLATIONAL PROCESSING 

809
00:41:16,348 --> 00:41:21,286
WHERE IT HAS AS ITS C TERMINUS A

810
00:41:21,286 --> 00:41:24,489
HYDROPHOBIC TAIL AND THERE'S A 

811
00:41:24,489 --> 00:41:25,691
CLEAVAGE PROCESS THAT COMES 

812
00:41:25,691 --> 00:41:28,827
ALONG AND REMOVES THAT SO MATURE

813
00:41:28,827 --> 00:41:30,896
LAMIN A IN THE LOWER LEFT IS NO 

814
00:41:30,896 --> 00:41:31,530
LONGER ANCHORED BY THE 

815
00:41:31,530 --> 00:41:33,432
PARTICULAR TAIL.

816
00:41:33,432 --> 00:41:34,967
SO WHAT IS THAT DOING?

817
00:41:34,967 --> 00:41:36,835
WE THINK THE REASON IT'S THERE 

818
00:41:36,835 --> 00:41:38,136
IS IT'S KIND OF A ZIP CODE.

819
00:41:38,136 --> 00:41:40,639
THIS PROTEIN NEEDS TO LIVE ON 

820
00:41:40,639 --> 00:41:44,209
THE INNER SURFACE OF THE NUCLEAR

821
00:41:44,209 --> 00:41:46,211
SCAFFOLD UNDER THE NUCLEAR 

822
00:41:46,211 --> 00:41:48,180
MEMBRANE AND THE TAIL HELPS IT 

823
00:41:48,180 --> 00:41:51,583
GETS THERE BUT THEN YOU WANT IT 

824
00:41:51,583 --> 00:41:53,485
RELEASED OTHER WISE OTHER 

825
00:41:53,485 --> 00:41:54,786
PROTEINS ARE STUCK TOO AND SOON 

826
00:41:54,786 --> 00:41:58,023
YOU HAVE DONE A BAD THING TO THE

827
00:41:58,023 --> 00:41:58,423
NUCLEAR STRUCTURE.

828
00:41:58,423 --> 00:42:01,994
WITH THE PROGERIA MUTATION, 

829
00:42:01,994 --> 00:42:05,597
THOSE 50 AMINO ACIDS CONTAIN THE

830
00:42:05,597 --> 00:42:10,369
RECOGNITION SITE FOR THE ENZYME 

831
00:42:10,369 --> 00:42:13,405
CALLED ZMC24 AND CAN'T BE 

832
00:42:13,405 --> 00:42:20,579
RECOGNIZED AND YOU NO CLEAVAGE 

833
00:42:20,579 --> 00:42:23,148
AND HAVE A PERMANENT LAMIN A AND

834
00:42:23,148 --> 00:42:23,615
CAUSES HAVOC.

835
00:42:23,615 --> 00:42:24,850
THAT'S A GOOD SUMMARY OF WHAT WE

836
00:42:24,850 --> 00:42:27,986
THINK THE MECHANISM IS.

837
00:42:27,986 --> 00:42:30,188
WHAT YOU SEE, YOU CAN SEE A 

838
00:42:30,188 --> 00:42:33,458
COUPLE CELLS ON THE LOWER LEFT 

839
00:42:33,458 --> 00:42:35,560
IS NORMAL CELL STAINED WITH 

840
00:42:35,560 --> 00:42:37,296
LAMIN A.

841
00:42:37,296 --> 00:42:38,830
IT'S NICE OVAL SHAPE.

842
00:42:38,830 --> 00:42:41,166
ON THE RIGHT IS A PROGERIA CELL 

843
00:42:41,166 --> 00:42:43,335
THAT'S GONE THROUGH A FEW 

844
00:42:43,335 --> 00:42:46,004
PASSAGES AND NOT A NORMAL 

845
00:42:46,004 --> 00:42:47,572
LOOKING NUCLEUS AND IRREGULAR 

846
00:42:47,572 --> 00:42:49,007
AND HAS WEBBING BECAUSE THE 

847
00:42:49,007 --> 00:42:51,576
STRUCTURE HAS BEEN DISTURBED BY 

848
00:42:51,576 --> 00:42:55,013
THESE PROTEINS WHICH IN THE 

849
00:42:55,013 --> 00:42:58,583
UPPER DIAGRAM ARE SHOWN AS GREEN

850
00:42:58,583 --> 00:43:00,819
CANDLE STICKS WITH THE OVAL 

851
00:43:00,819 --> 00:43:03,021
STUCK IN THE MEMBRANE AND THE 

852
00:43:03,021 --> 00:43:04,589
OTHER THINGS HAPPEN AS A RESULT 

853
00:43:04,589 --> 00:43:04,957
OF THAT.

854
00:43:04,957 --> 00:43:09,394
YOU GET WEBBING IN THE NUCLEUS 

855
00:43:09,394 --> 00:43:11,430
AND CHROM CHROMATIN 

856
00:43:11,430 --> 00:43:12,764
DISORGANIZATION AND LAMIN A 

857
00:43:12,764 --> 00:43:14,800
PLAYS A ROLE INSIDE THE NUCLEUS 

858
00:43:14,800 --> 00:43:19,538
AND OVER ALL YOU GET EARLY 

859
00:43:19,538 --> 00:43:20,639
REPLICATED SENESCENCE.

860
00:43:20,639 --> 00:43:23,508
YOU IF TAKE A FIBROBLAST WITH A 

861
00:43:23,508 --> 00:43:27,312
PERSON FROM PROGERIA IT WILL 

862
00:43:27,312 --> 00:43:28,747
SENESCE LONG BEFORE SOMEBODY WHO

863
00:43:28,747 --> 00:43:29,982
DOESN'T HAVE THIS CONDITION.

864
00:43:29,982 --> 00:43:32,117
QUICKLY, WE HAD A GOOD IDEA OF 

865
00:43:32,117 --> 00:43:33,685
THE BIOLOGICAL PROBLEM.

866
00:43:33,685 --> 00:43:35,120
WHAT ARE WE GOING DO ABOUT IT?

867
00:43:35,120 --> 00:43:36,922
WE FIGURED IF WE WANT TO 

868
00:43:36,922 --> 00:43:37,956
UNDERSTAND THIS AND MOVE IT IN 

869
00:43:37,956 --> 00:43:39,157
THE DIRECTION OF ANY KIND OF 

870
00:43:39,157 --> 00:43:41,593
THERAPY, WE NEED AN ANIMAL 

871
00:43:41,593 --> 00:43:43,562
MODEL.

872
00:43:43,562 --> 00:43:45,397
WE WANTED AN ANIMAL MODEL AS 

873
00:43:45,397 --> 00:43:46,999
CLOSE AS POSSIBLE TO THE HUMAN 

874
00:43:46,999 --> 00:43:47,265
CONDITION.

875
00:43:47,265 --> 00:43:50,369
WE COULD HAVE GONE IN AND MUTATE

876
00:43:50,369 --> 00:44:00,212
THE MOUSE LAMINATED GENE AND OUR

877
00:44:00,212 --> 00:44:01,913
MODEL HAS THE HUMAN GENE 

878
00:44:01,913 --> 00:44:03,048
INSERTED INTO IT.

879
00:44:03,048 --> 00:44:04,683
IT'S A TRANSGENIC.

880
00:44:04,683 --> 00:44:07,085
BUT WE WANTED THE TRANSGENIC TO 

881
00:44:07,085 --> 00:44:09,087
CARRY ALONG WITH IT THE 

882
00:44:09,087 --> 00:44:12,991
REGULATORY SIGNALS FOR LAMIN A 

883
00:44:12,991 --> 00:44:15,660
AND GET EXPRESSED IN THE RIGHT 

884
00:44:15,660 --> 00:44:19,798
TIME OR TISSUE AND BIG PIECE OF 

885
00:44:19,798 --> 00:44:28,940
DNA AND RETRO ENGINEERED WITH 

886
00:44:28,940 --> 00:44:32,010
G6O8G WHICH IS WHAT WE CALL IT 

887
00:44:32,010 --> 00:44:34,579
AND ACTING THE SPLICE DONOR.

888
00:44:34,579 --> 00:44:37,783
THIS MOUSE MODEL WE'VE HAD IN 

889
00:44:37,783 --> 00:44:42,087
THE LAB QUITE A LONG TIME GOING 

890
00:44:42,087 --> 00:44:43,555
ON 15 YEARS HAS BEEN A SOURCE OF

891
00:44:43,555 --> 00:44:45,724
EXPERIMENTS WE CAN DO TO ASSESS 

892
00:44:45,724 --> 00:44:46,758
THE ACTUAL CAUSE AND MOST 

893
00:44:46,758 --> 00:44:47,492
IMPORTANTLY WHAT KINDS OF 

894
00:44:47,492 --> 00:44:50,796
THERAPIES MIGHT HELP.

895
00:44:50,796 --> 00:44:52,431
YOU CAN SEE WHAT THE MICE LOOK 

896
00:44:52,431 --> 00:44:54,599
LIKE BUT YOU WANT TO SEE THE 

897
00:44:54,599 --> 00:44:56,835
PHENOTYPE COME ON AS EARLY AS 

898
00:44:56,835 --> 00:44:58,070
POSSIBLE.

899
00:44:58,070 --> 00:45:03,575
WE BREED THESE NICE TO 

900
00:45:03,575 --> 00:45:11,183
HOMOZYGOUS  AND THIS IS IN BAD 

901
00:45:11,183 --> 00:45:12,884
SHAPE AND THE MOUSE WILL NOT 

902
00:45:12,884 --> 00:45:14,920
LIVE MORE THAN ANOTHER WEEK OR 

903
00:45:14,920 --> 00:45:15,320
SO.

904
00:45:15,320 --> 00:45:16,188
COMPARED TO WILD TYPE THEY'RE 

905
00:45:16,188 --> 00:45:18,156
SMALL AND BY THE TIME THEY GET 

906
00:45:18,156 --> 00:45:20,392
TO FIVE TO SIX MONTHS THEY'RE 

907
00:45:20,392 --> 00:45:21,159
CLEARLY SHOWING A LOT OF THE 

908
00:45:21,159 --> 00:45:23,562
SIGNS OF PROGERIA AND 

909
00:45:23,562 --> 00:45:24,863
IMPORTANTLY THAT INCLUDES THE 

910
00:45:24,863 --> 00:45:25,630
CARDIOVASCULAR DISEASE AS I'LL 

911
00:45:25,630 --> 00:45:26,932
SHOW IN A MINUTE.

912
00:45:26,932 --> 00:45:28,900
THIS IS A PRETTY DARN GOOD MODEL

913
00:45:28,900 --> 00:45:30,035
OF THE HUMAN DISEASE.

914
00:45:30,035 --> 00:45:32,037
IT DOESN'T ALWAYS WORK THAT WAY 

915
00:45:32,037 --> 00:45:33,738
WHEN YOU MAKE A MOUSE THEN YOU 

916
00:45:33,738 --> 00:45:36,241
TRY TO CREATE A MUTATION THAT 

917
00:45:36,241 --> 00:45:38,810
OUGHT TO BE THE SAME OF THE 

918
00:45:38,810 --> 00:45:39,911
HUMAN SOMETIMES NOT SO MUCH BUT 

919
00:45:39,911 --> 00:45:42,747
WE HAVE A GOOD OPPORTUNITY TO DO

920
00:45:42,747 --> 00:45:43,582
WORK WITH A MODEL SIMILAR TO THE

921
00:45:43,582 --> 00:45:48,954
HUMAN.

922
00:45:48,954 --> 00:45:49,387
WHAT HAPPENS IN THE 

923
00:45:49,387 --> 00:45:50,922
CARDIOVASCULAR SYSTEM.

924
00:45:50,922 --> 00:45:51,590
PROBABLY NOT A LOT OF YOU ARE 

925
00:45:51,590 --> 00:45:55,360
USED TO LOOKING AT SECTIONS OF 

926
00:45:55,360 --> 00:45:56,895
THE AORTA IN THE MOUSE AND THIS 

927
00:45:56,895 --> 00:45:58,530
IS WHERE A LOT OF THE MOST 

928
00:45:58,530 --> 00:46:00,999
SEVERE DAMAGE HAPPENS IS IN 

929
00:46:00,999 --> 00:46:06,938
LARGE VESSELS AND THE A -- AORTA

930
00:46:06,938 --> 00:46:09,474
IS THE LARGEST VESSEL.

931
00:46:09,474 --> 00:46:10,675
THESE HAVE SIX-MONTH-OLD MICE.

932
00:46:10,675 --> 00:46:15,580
THE COLUMN ON THE RIGHT IS THE 

933
00:46:15,580 --> 00:46:19,184
DOUBLE COPY HOMOZYGOUS GENE AND 

934
00:46:19,184 --> 00:46:20,185
I DON'T THINK YOU CAN SEE ALL 

935
00:46:20,185 --> 00:46:23,588
THE DETAILS BUT YOU CAN SEE THIS

936
00:46:23,588 --> 00:46:26,725
EXTENSIVE THICKENING OF THE 

937
00:46:26,725 --> 00:46:28,460
OUTSIDE OF THE VESSEL IN THE 

938
00:46:28,460 --> 00:46:30,529
NORMAL THAT'S NOT ALL THERE AND 

939
00:46:30,529 --> 00:46:32,564
THIS IS WHAT WAS MENTIONED AND 

940
00:46:32,564 --> 00:46:35,167
HERE IT'S VERY THICK AND THAT'S 

941
00:46:35,167 --> 00:46:36,735
THE HALLMARK OF THIS IN THE 

942
00:46:36,735 --> 00:46:38,203
MOUSE AND HUMAN CONDITION.

943
00:46:38,203 --> 00:46:40,372
IF YOU LOOKED AT A HIGHER LEVEL 

944
00:46:40,372 --> 00:46:42,140
RESOLUTION YOU'D ALSO SEE 

945
00:46:42,140 --> 00:46:43,909
SOMETHING PROFOUND THAT IS THE 

946
00:46:43,909 --> 00:46:46,545
MEDIAL LEVEL LAYER OF THE AORTA 

947
00:46:46,545 --> 00:46:51,850
WHICH IS WHERE THE SMOOTH MUSCLE

948
00:46:51,850 --> 00:46:56,388
CELLS ARE ACELLULAR AND IT'S THE

949
00:46:56,388 --> 00:46:57,522
VASCULAR SMOOTH MUSCLE CELLS 

950
00:46:57,522 --> 00:47:03,061
WITH THE GREATEST SENSITIVITY TO

951
00:47:03,061 --> 00:47:05,297
PROGERRIN AND THEY DISAPPEAR AND

952
00:47:05,297 --> 00:47:10,502
THIS IS A CELLULAR AND PRONE TO 

953
00:47:10,502 --> 00:47:11,136
ATHEROSCLEROSIS OF STROKES IN 

954
00:47:11,136 --> 00:47:12,704
HEART ATTACKS IN KIDS ARE THE 

955
00:47:12,704 --> 00:47:15,774
SAME THING THAT NOW HAPPEN IN 

956
00:47:15,774 --> 00:47:16,041
THE MOUSE.

957
00:47:16,041 --> 00:47:25,884
AGAIN, A GOOD MODEL.

958
00:47:25,884 --> 00:47:27,819
PEOPLE HAVE DONE WORK ON LAMIN A

959
00:47:27,819 --> 00:47:29,154
BIOLOGY SO WE HAD SOMETHING 

960
00:47:29,154 --> 00:47:31,423
GOING AND MAYBE WE CAN DIAL BACK

961
00:47:31,423 --> 00:47:33,325
THE AMOUNT OF THE TOXIC PROTEIN 

962
00:47:33,325 --> 00:47:37,329
BY BLOCKING THE STEP FOR WHICH 

963
00:47:37,329 --> 00:47:38,230
ACTUALLY A KNOWN CLASS OF DRUGS 

964
00:47:38,230 --> 00:47:43,168
ALREADY HAD BEEN DEVELOPED.

965
00:47:43,168 --> 00:47:46,104
THOSE ARE TRANSFERASES.

966
00:47:46,104 --> 00:47:51,576
THEY NORMALLY ATTACH AND THERE 

967
00:47:51,576 --> 00:47:55,580
ARE TRANSFERASE INHIBITORS BEING

968
00:47:55,580 --> 00:47:59,584
DEVELOPED BECAUSE THE ONCA 

969
00:47:59,584 --> 00:48:01,720
PROTEIN AND THEY THOUGHT THEY 

970
00:48:01,720 --> 00:48:04,756
COULD CURE CANCER AND FOR 

971
00:48:04,756 --> 00:48:07,058
COMPLICATED IT DOES NOT WORK FOR

972
00:48:07,058 --> 00:48:08,526
RAS AND CANCER APPLICATIONS BUT 

973
00:48:08,526 --> 00:48:10,295
WE SAID LET'S TRY AND SEE.

974
00:48:10,295 --> 00:48:12,130
WE DON'T EXPECT THIS TO BE A 

975
00:48:12,130 --> 00:48:12,964
CURE BECAUSE YOU'RE DIALING BACK

976
00:48:12,964 --> 00:48:16,501
THE AMOUNT OF PROGERIN AND NOT 

977
00:48:16,501 --> 00:48:20,305
ELIMINATING IT AND YOU WORRY 

978
00:48:20,305 --> 00:48:21,740
ABOUT TOXICITY BECAUSE YOU'RE 

979
00:48:21,740 --> 00:48:23,608
AFFECTING ALL PROTEINS IN SOME 

980
00:48:23,608 --> 00:48:26,945
WAY AND THE FIRST CELL 

981
00:48:26,945 --> 00:48:29,748
EXPERIMENT UP ON THE FIFTH FLOOR

982
00:48:29,748 --> 00:48:32,984
HERE AS A TRAINEE SHOWED 

983
00:48:32,984 --> 00:48:34,819
REMARKABLE RESULTS IN THIS SPACE

984
00:48:34,819 --> 00:48:35,920
OF 72 HOURS.

985
00:48:35,920 --> 00:48:38,356
TWO DIFFERENT PROGERIA CELL 

986
00:48:38,356 --> 00:48:41,393
LINES SHOWING EITHER ONE OR TWO 

987
00:48:41,393 --> 00:48:48,033
MICROMOLAR OF A TRANSFERASE 

988
00:48:48,033 --> 00:48:58,543
INHIBITER NUCLEIZED THE SHAPE 

989
00:49:00,945 --> 00:49:02,547
AND THIS SHOWS MORE DETAILS 

990
00:49:02,547 --> 00:49:03,348
ABOUT THE CELLS.

991
00:49:03,348 --> 00:49:11,156
LOOK FIRST AT THE UPPER ROW.

992
00:49:11,156 --> 00:49:12,924
THE WILD TYPE MICE AND YOU CAN 

993
00:49:12,924 --> 00:49:20,799
SEE THE PINK GLOBULES ARE NUCLEI

994
00:49:20,799 --> 00:49:22,267
IN THE VASCULAR SMOOTH MUSCLE 

995
00:49:22,267 --> 00:49:24,402
CELLS AND THE GREEN STUFF IS 

996
00:49:24,402 --> 00:49:27,572
SMOOTH MUSCLE ALPHA ACTIN THE 

997
00:49:27,572 --> 00:49:29,908
PROTEINS THE CELLS DEPEND ON.

998
00:49:29,908 --> 00:49:32,844
THIS IS A HEALTHY LOOKING AORTA.

999
00:49:32,844 --> 00:49:34,846
NOW LOOK AT THE PROGERIA.

1000
00:49:34,846 --> 00:49:35,680
LIKE I SAID THE CELLS ARE JUST 

1001
00:49:35,680 --> 00:49:38,183
GONE.

1002
00:49:38,183 --> 00:49:41,953
THERE ARE NO NUCLEI TO SPEAK OF.

1003
00:49:41,953 --> 00:49:45,256
YOU CAN SEE IT'S STAINED WITH 

1004
00:49:45,256 --> 00:49:47,359
PROGERIN THERE'S SOME GHOSTS 

1005
00:49:47,359 --> 00:49:49,728
LEFT BEHIND WHERE MAYBE THERE 

1006
00:49:49,728 --> 00:49:52,764
WERE ONCE NUCLEI BUT THEY'RE 

1007
00:49:52,764 --> 00:49:56,267
GONE AND IT'S A WASTELAND.

1008
00:49:56,267 --> 00:50:01,473
YOU SEE THE SQUIGGLY GREEN GUYS.

1009
00:50:01,473 --> 00:50:03,007
WHAT HAPPENS IF YOU TREAT THE 

1010
00:50:03,007 --> 00:50:06,711
MOUSE STARTING AT AN EARLY AGE 

1011
00:50:06,711 --> 00:50:11,182
WITH A TRANSFERASE INHIBITOR.

1012
00:50:11,182 --> 00:50:14,386
CHECK IT OUT.

1013
00:50:14,386 --> 00:50:16,354
THIS SHOWS YOU AT THE SAME POINT

1014
00:50:16,354 --> 00:50:19,557
AT NINE MONTHS YOU COULD 

1015
00:50:19,557 --> 00:50:21,393
ESSENTIALLY PRESERVE THE 

1016
00:50:21,393 --> 00:50:23,194
ARCHITECTURE OF THE AORTA.

1017
00:50:23,194 --> 00:50:24,262
NOT QUITE ENTIRELY.

1018
00:50:24,262 --> 00:50:26,297
YOU CAN SEE SOME PLACES WHERE 

1019
00:50:26,297 --> 00:50:27,832
YOU DON'T HAVE AS MANY NUCLEIS 

1020
00:50:27,832 --> 00:50:29,033
AS YOU SHOULD BUT IT'S LOOKING 

1021
00:50:29,033 --> 00:50:33,004
LIKE A GOOD IDEA.

1022
00:50:33,004 --> 00:50:34,606
OKAY, WE'RE ON THE RIGHT PATH 

1023
00:50:34,606 --> 00:50:37,876
BUT WE'RE A BASIC SCIENCE LAB.

1024
00:50:37,876 --> 00:50:40,445
WE DO GOOD CELL BIOLOGY AND 

1025
00:50:40,445 --> 00:50:43,348
MOLECULAR GENETICS AND WHAT WE 

1026
00:50:43,348 --> 00:50:44,916
WANT TO DO IS WILL THIS BENEFIT 

1027
00:50:44,916 --> 00:50:47,725
A PATIENT.

1028
00:50:47,725 --> 00:50:49,393
THAT'S WHERE I HAVE TO TALK TO 

1029
00:50:49,393 --> 00:50:52,563
MY FRIEND LESLIE AND SAY, OKAY, 

1030
00:50:52,563 --> 00:50:54,698
IS IT POSSIBLE WE MIGHT ACTUALLY

1031
00:50:54,698 --> 00:50:57,868
MOUNT A CLINICAL TRIAL WITH THIS

1032
00:50:57,868 --> 00:50:58,235
CLASS OF DRUGS?

1033
00:50:58,235 --> 00:51:01,372
HOW IN THE WORLD YOU WOULD DO 

1034
00:51:01,372 --> 00:51:02,206
THAT WITH SUCH A RARE DISEASE 

1035
00:51:02,206 --> 00:51:04,108
WITH KIDS ALL OVER THE WORLD?

1036
00:51:04,108 --> 00:51:05,376
HOW WOULD YOU DO THAT?

1037
00:51:05,376 --> 00:51:06,911
>> BEFORE WE GET TO THAT
I'D 

1038
00:51:06,911 --> 00:51:09,280
LIKE TO ASK YOU A QUESTION.

1039
00:51:09,280 --> 00:51:11,015
HOW DID YOU FEEL -- YOU 

1040
00:51:11,015 --> 00:51:12,750
DISCOVERED THE GENE -- I GUESS 

1041
00:51:12,750 --> 00:51:17,455
OUR TEAM, BUT YOU LED THIS 

1042
00:51:17,455 --> 00:51:17,721
DISCOVERY.

1043
00:51:17,721 --> 00:51:22,393
YOU HADN'T EVEN FINISHED THE 

1044
00:51:22,393 --> 00:51:24,094
HUMAN GENOME PROJECT AND WERE 

1045
00:51:24,094 --> 00:51:25,162
75% OR SO THROUGH.

1046
00:51:25,162 --> 00:51:26,530
HOW DID YOU FEEL AND WHAT WERE 

1047
00:51:26,530 --> 00:51:28,065
YOUR HOPES?

1048
00:51:28,065 --> 00:51:31,469
WHAT DID YOU THINK?

1049
00:51:31,469 --> 00:51:33,771
FRANCIS: THIS WAS AN AMAZING 

1050
00:51:33,771 --> 00:51:35,539
COMPELLING OPPORTUNITY AS A 

1051
00:51:35,539 --> 00:51:39,710
SCIENTIST TO DO INTERESTING 

1052
00:51:39,710 --> 00:51:42,313
DETECTIVE WORK TO SORT OUT THE 

1053
00:51:42,313 --> 00:51:43,013
CAUSE OF THE DISEASE.

1054
00:51:43,013 --> 00:51:44,849
RECOGNIZE THIS WAS A HARD ONE TO

1055
00:51:44,849 --> 00:51:46,183
FIGURE OUT BECAUSE IT DOESN'T 

1056
00:51:46,183 --> 00:51:50,588
RUN IN FAMILIES SO THE THINGS 

1057
00:51:50,588 --> 00:51:52,823
GENETICISTS DO WASN'T AVAILABLE 

1058
00:51:52,823 --> 00:51:54,725
AND FINDING THE STRAIN WAS AN 

1059
00:51:54,725 --> 00:52:02,399
ARTICLE IT WAS ACADEMICALLY AND 

1060
00:52:02,399 --> 00:52:05,035
INTELLECTUALLY CHALLENGING BUT 

1061
00:52:05,035 --> 00:52:06,971
ABOUT TRYING TO FIND KIDS LIKE 

1062
00:52:06,971 --> 00:52:10,174
SAM AND CASEY WHEN I WAS A 

1063
00:52:10,174 --> 00:52:13,310
FELLOW IN 1983 WITH THE SAME 

1064
00:52:13,310 --> 00:52:14,044
DIAGNOSIS AND I FELT POWERLESS 

1065
00:52:14,044 --> 00:52:14,845
BECAUSE I DIDN'T KNOW ANYTHING 

1066
00:52:14,845 --> 00:52:17,281
ABOUT IT OR WHAT TO DO TO HELP.

1067
00:52:17,281 --> 00:52:19,016
AS A PHYSICIAN SCIENTIST YOU 

1068
00:52:19,016 --> 00:52:25,422
DREAM OF A DAY WHERE YOU HAVE A 

1069
00:52:25,422 --> 00:52:31,462
COMBINATION OF SOMETHING 

1070
00:52:31,462 --> 00:52:33,764
SCIENTIFICALLY CHALLENGING AND 

1071
00:52:33,764 --> 00:52:34,398
THIS WAS A PARTICULAR COMPELLING

1072
00:52:34,398 --> 00:52:42,840
ONE.

1073
00:52:42,840 --> 00:52:43,374
THANK YOU.

1074
00:52:43,374 --> 00:52:44,675
THAT WAS GREAT TO HEAR.

1075
00:52:44,675 --> 00:52:45,576
THIS IS WHERE THE HUMAN BRIDGE 

1076
00:52:45,576 --> 00:52:55,753
COMES IN.

1077
00:53:03,327 --> 00:53:07,364
TODAY THERE ARE 16 KIDS IN THE 

1078
00:53:07,364 --> 00:53:08,299
U.S.

1079
00:53:08,299 --> 00:53:10,134
WE HAD BEEN BUILDING THIS 

1080
00:53:10,134 --> 00:53:11,368
REGISTRY AND KEEPING IN TOUCH 

1081
00:53:11,368 --> 00:53:13,404
WITH FAMILIES AND BUILDING A 

1082
00:53:13,404 --> 00:53:14,438
FAMILY HISTORY OF CLINICAL 

1083
00:53:14,438 --> 00:53:14,838
CHARTS.

1084
00:53:14,838 --> 00:53:19,643
WE WERE GOING TO MAKE A LEAP.

1085
00:53:19,643 --> 00:53:21,312
I DON'T REMEMBER DOUBTING WE'D 

1086
00:53:21,312 --> 00:53:23,847
DO THIS SO THAT'S WHAT WE DID.

1087
00:53:23,847 --> 00:53:29,420
WE STARTED FIRST HERE AT THE 

1088
00:53:29,420 --> 00:53:30,788
CLINICAL CENTER WITH A NATURAL 

1089
00:53:30,788 --> 00:53:32,723
HISTORY STUDY THAT GRADUATES YOU

1090
00:53:32,723 --> 00:53:35,893
FROM CLINICAL CHARTS TO SEEING A

1091
00:53:35,893 --> 00:53:41,465
SERIES OF EIGHT OR NINE KIDS A 

1092
00:53:41,465 --> 00:53:42,800
SERIES OF INVESTIGATING THE 

1093
00:53:42,800 --> 00:53:43,901
NATURAL HISTORY BECAUSE NOBODY 

1094
00:53:43,901 --> 00:53:46,203
KNEW WHAT IT WAS FROM AN 

1095
00:53:46,203 --> 00:53:49,373
OBJECTIVE PERSPECTIVE AND 

1096
00:53:49,373 --> 00:53:51,308
OUTCOME MEASURES AND OBJECTIVE 

1097
00:53:51,308 --> 00:53:54,678
MEASURES OF SUCCESS WOULDN'T BE 

1098
00:53:54,678 --> 00:53:55,579
POSSIBLE WAY BACK THEN WITHOUT 

1099
00:53:55,579 --> 00:54:00,951
SUCCESS AND THEN WE FOUND THE 

1100
00:54:00,951 --> 00:54:11,495
WORLD'S LEADER IN LONFARNIB AND 

1101
00:54:11,929 --> 00:54:14,098
I HAD AN AMAZING COLLEAGUE I 

1102
00:54:14,098 --> 00:54:15,833
HAVE TO CALL OUT BECAUSE SHE HAD

1103
00:54:15,833 --> 00:54:18,702
BEEN INVOLVED WITH AND LEAD WITH

1104
00:54:18,702 --> 00:54:19,870
EARLY DAYS.

1105
00:54:19,870 --> 00:54:21,772
THESE CLINICAL TRIALS ALL SEEN 

1106
00:54:21,772 --> 00:54:26,410
HERE.

1107
00:54:26,410 --> 00:54:28,078
WE LAUNCHED THE FIRST CLINICAL 

1108
00:54:28,078 --> 00:54:31,048
TRIAL FOR PROGERIA AND BOSTON 

1109
00:54:31,048 --> 00:54:33,050
CHILDREN'S HOSPITAL WHILE 

1110
00:54:33,050 --> 00:54:33,884
BUILDING THIS TEAM OF EXPERTS 

1111
00:54:33,884 --> 00:54:35,919
THEY WERE NOW THE WORLD'S 

1112
00:54:35,919 --> 00:54:37,921
EXPERTS BECAUSE NOBODY WAS THE 

1113
00:54:37,921 --> 00:54:41,792
WORLD'S EXPERT AND THEY REMAINED

1114
00:54:41,792 --> 00:54:48,866
SO.

1115
00:54:48,866 --> 00:54:52,803
AND WE WANT TO GET THE WORD OUT.

1116
00:54:52,803 --> 00:54:55,739
SO WE HAD A SERIES AND IF YOU'LL

1117
00:54:55,739 --> 00:55:01,145
NOTE IN ALL THE CLINICAL TRIALS,

1118
00:55:01,145 --> 00:55:03,047
LONAFARNIB IS THE COMMON 

1119
00:55:03,047 --> 00:55:05,015
DENOMINATOR AND KEPT IT ON BOARD

1120
00:55:05,015 --> 00:55:06,283
FROM 2007 TO NOW AND THAT WILL 

1121
00:55:06,283 --> 00:55:08,852
BE IMPORTANT TO WHAT I TELL YOU 

1122
00:55:08,852 --> 00:55:09,053
NEXT.

1123
00:55:09,053 --> 00:55:10,254
WE BROUGHT THE CHILDREN IN 

1124
00:55:10,254 --> 00:55:10,454
PAIRS.

1125
00:55:10,454 --> 00:55:13,390
WE STILL DO AND THEIR FAMILIES 

1126
00:55:13,390 --> 00:55:21,765
BECAUSE A WEEK OF TEST IING AN  

1127
00:55:21,765 --> 00:55:23,067
COUNTRY WHERE YOU DON'T SPEAK 

1128
00:55:23,067 --> 00:55:24,168
THE LANGUAGE IS DIFFICULT TO THE

1129
00:55:24,168 --> 00:55:26,470
KIDS AND FAMILIES SUPPORT EACH 

1130
00:55:26,470 --> 00:55:26,804
OTHER.

1131
00:55:26,804 --> 00:55:28,138
MAYBE SAMMY WILL TALK ABOUT THAT

1132
00:55:28,138 --> 00:55:30,107
AFTER I FINISH THIS SESSION.

1133
00:55:30,107 --> 00:55:31,075
AFTER TWO YEARS OF TREATMENT WE 

1134
00:55:31,075 --> 00:55:37,781
HAD EVIDENCE.

1135
00:55:37,781 --> 00:55:39,717
WE WERE WORKING OUT THE HISTORY 

1136
00:55:39,717 --> 00:55:47,858
AND THE VASCULAR STIFFNESS 

1137
00:55:47,858 --> 00:55:49,393
WASN'T KNOWN AND WE FOUND AN 

1138
00:55:49,393 --> 00:55:51,395
INCREASE AND MOST IMPORTANTLY, 

1139
00:55:51,395 --> 00:55:52,096
CARDIOVASCULAR STIFFNESS AND 

1140
00:55:52,096 --> 00:55:56,333
I'LL SHOW A COUPLE SLIDES WAS 

1141
00:55:56,333 --> 00:55:56,600
IMPROVED.

1142
00:55:56,600 --> 00:55:58,702
BONE STRUCTURE NOT THE DENSITY 

1143
00:55:58,702 --> 00:56:00,704
BECAUSE THE DENSITY'S PRETTY 

1144
00:56:00,704 --> 00:56:03,474
OKAY BUT THE BONE STRUCTURE GOT 

1145
00:56:03,474 --> 00:56:06,076
MORE TOLERANT TO BENDING AND 

1146
00:56:06,076 --> 00:56:07,878
TWISTING AND SOME HEARING 

1147
00:56:07,878 --> 00:56:08,212
IMPROVEMENTS.

1148
00:56:08,212 --> 00:56:13,684
OTHER THINGS WERE NOT AFFECTED.

1149
00:56:13,684 --> 00:56:24,228
WE DIDN'T IMPROVE THE THAT'S 

1150
00:56:24,228 --> 00:56:25,395
WHAT WE WERE GOING FOR WITH THE 

1151
00:56:25,395 --> 00:56:34,605
CURE.

1152
00:56:34,605 --> 00:56:35,239
THE CARDIOVASCULAR MEASURE OF 

1153
00:56:35,239 --> 00:56:37,474
THE INTEGRITY OF THE STIFFNESS 

1154
00:56:37,474 --> 00:56:41,211
OR FLEXIBILITY OF YOUR BLOOD 

1155
00:56:41,211 --> 00:56:43,480
VESSELS WAS IMPROVED AND THIS 

1156
00:56:43,480 --> 00:56:48,819
WAS A DISCOVERY LED AT THE 

1157
00:56:48,819 --> 00:56:51,188
BRIGHAM AND WOMEN'S SO PULSE 

1158
00:56:51,188 --> 00:56:53,190
WAVE VELOCITY MEASURES 

1159
00:56:53,190 --> 00:56:53,457
STIFFNESS.

1160
00:56:53,457 --> 00:56:55,325
A HIGHER NUMBER IS NOT GOOD.

1161
00:56:55,325 --> 00:56:56,994
A LOWER NUMBER SAY BETTER NUMBER

1162
00:56:56,994 --> 00:57:01,098
AND ALL BUT ONE OF THE KIDS 

1163
00:57:01,098 --> 00:57:01,799
DECREASED BY A LOT OF.

1164
00:57:01,799 --> 00:57:04,668
AND THE DECREASE THEY 

1165
00:57:04,668 --> 00:57:07,905
EXPERIENCED WAS -- IF YOU 

1166
00:57:07,905 --> 00:57:10,507
DECREASE ONE METER PER SECOND IN

1167
00:57:10,507 --> 00:57:15,279
THE ADULT POPULATION THE CHANCE 

1168
00:57:15,279 --> 00:57:16,246
DECREASE AND THIS IS 3 1/2.

1169
00:57:16,246 --> 00:57:17,781
I REMEMBER THE DAY WE FOUND 

1170
00:57:17,781 --> 00:57:21,785
THIS.

1171
00:57:21,785 --> 00:57:23,921
I WAS LIKE DID IT REALLY WORK?

1172
00:57:23,921 --> 00:57:25,789
THIS WAS THE FUNCTIONAL MEASURE 

1173
00:57:25,789 --> 00:57:28,792
OF VASCULAR PATHOLOGY AND THIS 

1174
00:57:28,792 --> 00:57:30,794
IS THE ACTUAL ULTRASOUND AND 

1175
00:57:30,794 --> 00:57:35,432
WHAT YOU'RE SEEING IS THE WALL 

1176
00:57:35,432 --> 00:57:37,267
OF THE VESSEL, THE OF THE ARTERY

1177
00:57:37,267 --> 00:57:39,036
FRANCIS WAS SHOWING YOU FROM THE

1178
00:57:39,036 --> 00:57:41,672
MICE AND BROUGHT IS BAD.

1179
00:57:41,672 --> 00:57:45,175
BRIGHT SHOWS YOU LESS CELLS, 

1180
00:57:45,175 --> 00:57:48,912
MORE COLLAGEN, MORE OF THOSE 

1181
00:57:48,912 --> 00:57:51,014
TYPES OF STIFF THINGS SO THIS IS

1182
00:57:51,014 --> 00:57:52,983
SOMEBODY NORMAL AND THIS IS 

1183
00:57:52,983 --> 00:57:54,818
SOMEBODY WITH PROGERIA AND A 

1184
00:57:54,818 --> 00:57:57,221
CHILD WITH PROGERIA AFTER 

1185
00:57:57,221 --> 00:57:58,322
TREATMENT.

1186
00:57:58,322 --> 00:57:59,590
OBVIOUSLY A LOT CLOSER TO NORMAL

1187
00:57:59,590 --> 00:58:00,424
THAN AT THE START.

1188
00:58:00,424 --> 00:58:03,560
THAT WAS REALLY EXCITING.

1189
00:58:03,560 --> 00:58:06,530
IT WASN'T ENOUGH FOR APPROVAL 

1190
00:58:06,530 --> 00:58:11,668
AND SO WE MOVED ON AND WHAT WE 

1191
00:58:11,668 --> 00:58:13,270
DID NEXT WAS LATE INCENTIVE.

1192
00:58:13,270 --> 00:58:15,505
WE MENTIONED TO THE FDA WE WERE 

1193
00:58:15,505 --> 00:58:17,774
TRYING TO LOOK AT LIFE SPAN AND 

1194
00:58:17,774 --> 00:58:20,878
THEY WERE EXCITED BY IT SO WE 

1195
00:58:20,878 --> 00:58:23,247
LOOKED AND LIFE SPAN DEATH WAS 

1196
00:58:23,247 --> 00:58:25,082
NOT A PART OF THE CLINICAL 

1197
00:58:25,082 --> 00:58:25,582
TRIALS OUTCOMES.

1198
00:58:25,582 --> 00:58:26,817
WE TOOK INFORMATION OVER THE 

1199
00:58:26,817 --> 00:58:28,986
YEARS OF BUILDING OUR REGISTRY, 

1200
00:58:28,986 --> 00:58:30,787
WE TOOK ALL OF THAT INFORMATION 

1201
00:58:30,787 --> 00:58:34,758
AND CREATED AN EXTERNAL BUT WELL

1202
00:58:34,758 --> 00:58:37,394
DEVISED CONTROL GROUP AND CAN 

1203
00:58:37,394 --> 00:58:43,667
CON -- COMPARE IT TO THE TRIAL 

1204
00:58:43,667 --> 00:58:45,702
KIDS AND ASK THE BENEFIT AND 

1205
00:58:45,702 --> 00:58:48,272
EVERY TIME YOU DRAW A CHILD 

1206
00:58:48,272 --> 00:58:48,572
PASSES AWAY.

1207
00:58:48,572 --> 00:58:52,109
THIS IS THE REGISTRY AND THE 

1208
00:58:52,109 --> 00:58:54,378
CHILDREN WHO DIDN'T GET IT AND 

1209
00:58:54,378 --> 00:58:54,945
THOSE THAT DID.

1210
00:58:54,945 --> 00:59:05,222
ONE DEATH VERSUS NINE.

1211
00:59:05,222 --> 00:59:08,458
THIS IS DATA THAT CAME LATER 

1212
00:59:08,458 --> 00:59:15,432
THAT LONAFARNIB IS EXTENDING 

1213
00:59:15,432 --> 00:59:18,669
LIFE SPAN BY AN AVERAGE OF 4.3 

1214
00:59:18,669 --> 00:59:20,237
YEARS FOR A 14-YEAR-OLD AVERAGE 

1215
00:59:20,237 --> 00:59:21,772
IS A LOT OF BUT CERTAINLY NOT 

1216
00:59:21,772 --> 00:59:23,206
FLUFF.

1217
00:59:23,206 --> 00:59:24,574
-- NOT ENOUGH.

1218
00:59:24,574 --> 00:59:30,247
SO WE WERE FORTUNATE ENOUGH TO 

1219
00:59:30,247 --> 00:59:38,789
BE GETTING DRUG FROM AND 

1220
00:59:38,789 --> 00:59:40,924
COLLABORATING ON AN AGREEMENT 

1221
00:59:40,924 --> 00:59:45,495
AND GOT APPROVAL IN 2020 IN THE 

1222
00:59:45,495 --> 00:59:46,596
U.S. AND 2022 IN EUROPE AND LAST

1223
00:59:46,596 --> 00:59:56,840
WEEK IN JAPAN.

1224
00:59:58,642 --> 01:00:00,477
WE HAVE TO CHANGE THE NUMBER OF 

1225
01:00:00,477 --> 01:00:10,754
APPROVED DRUGS.

1226
01:00:12,122 --> 01:00:12,756
SAMMY, TELL US MORE.

1227
01:00:12,756 --> 01:00:13,957
YOU WERE IN THE TRIAL FROM THE 

1228
01:00:13,957 --> 01:00:15,392
BEFORE HE BEGINNING.

1229
01:00:15,392 --> 01:00:19,396
TELL US ABOUT YOUR TRIAL 

1230
01:00:19,396 --> 01:00:19,696
EXPERIENCE.

1231
01:00:19,696 --> 01:00:27,738
IT WAS CRAZY.

1232
01:00:27,738 --> 01:00:30,974
WHEN I STARTED THE MEDICATION 

1233
01:00:30,974 --> 01:00:35,679
HERE ON THE LEFT I WAS JUST 12 

1234
01:00:35,679 --> 01:00:35,946
YEARS OLD.

1235
01:00:35,946 --> 01:00:42,953
SO I WAS A TEENAGER AND I WAS 

1236
01:00:42,953 --> 01:00:51,828
CHANGING I UNDERSTOOD I NEEDED 

1237
01:00:51,828 --> 01:00:52,029
HELP.

1238
01:00:52,029 --> 01:00:53,296
I UNDERSTOOD WHAT LIFE 

1239
01:00:53,296 --> 01:00:57,034
EXPECTANCY WAS IN REAL MATERIALS

1240
01:00:57,034 --> 01:01:03,807
AND WAS VERY ANGRY.

1241
01:01:03,807 --> 01:01:06,243
IT WAS UNFAIR AND I WAS ANGRY 

1242
01:01:06,243 --> 01:01:08,512
WITH GOD TOO AND AN THAT MOMENT 

1243
01:01:08,512 --> 01:01:13,550
ANGRY WITH GOD AS WELL.

1244
01:01:13,550 --> 01:01:16,987
PARADOXICALLY I WAS THINKING 

1245
01:01:16,987 --> 01:01:24,661
THEN TO TAKE SOMETHING TO BE 

1246
01:01:24,661 --> 01:01:27,064
BETTER GOES AGAINST GOD AND I 

1247
01:01:27,064 --> 01:01:28,165
WAS A TEENAGER AND I WAS 

1248
01:01:28,165 --> 01:01:38,708
CONFUSED AND IT WAS MESSY FOR ME

1249
01:01:56,026 --> 01:02:00,897
I REPUBLIC I DIDN'T WANT TO DO 

1250
01:02:00,897 --> 01:02:11,341
IT AND I REMEMBER WITH MY 

1251
01:02:34,965 --> 01:02:37,334
PARENTS AND I LOVE MY PARENTS.

1252
01:02:37,334 --> 01:02:41,938
THEY WANT ONLY THE BEST FOR ME.

1253
01:02:41,938 --> 01:02:46,309
THEN I LOOKED AT LESLIE AND SHE 

1254
01:02:46,309 --> 01:02:47,577
WAS LOOKING AT ME WITH THE SAME 

1255
01:02:47,577 --> 01:02:52,749
LOOK MY PARENTS WERE LOOKING TO 

1256
01:02:52,749 --> 01:02:52,916
ME.

1257
01:02:52,916 --> 01:02:58,088
BECAUSE FOR LESLIE WE ARE SONS 

1258
01:02:58,088 --> 01:03:01,024
AND DAUGHTERS AND IF SHE THINK 

1259
01:03:01,024 --> 01:03:04,961
THIS IS A GOOD THING, I BELIEVE 

1260
01:03:04,961 --> 01:03:05,195
IN HER.

1261
01:03:05,195 --> 01:03:07,898
I BELIEVE IN YOU AND THE SCIENCE

1262
01:03:07,898 --> 01:03:13,803
AND A STARTED TO TAKE IT AND I 

1263
01:03:13,803 --> 01:03:17,908
STARTED TO GROW INTERNALLY.

1264
01:03:17,908 --> 01:03:23,880
I UNDERSTOOD WHAT SCIENCE WAS 

1265
01:03:23,880 --> 01:03:33,957
A

1266
01:03:35,792 --> 01:03:37,527
AND UNDERSTAND SCIENCE WAS A 

1267
01:03:37,527 --> 01:03:43,099
GIFT FROM GOD AND AT THAT MOMENT

1268
01:03:43,099 --> 01:03:53,643
I STARTED TO SO UNDERSTAND AND I

1269
01:04:01,651 --> 01:04:03,153
WOULDN'T BE MORE GRATEFUL FOR 

1270
01:04:03,153 --> 01:04:13,530
THAT MOMENT I STARTED.

1271
01:04:13,930 --> 01:04:19,469
>> SAMMY YOU'VE GONE ON TO
DO 

1272
01:04:19,469 --> 01:04:20,437
OTHER THINGS AND YOU'RE ABLE 

1273
01:04:20,437 --> 01:04:22,205
AMBASSADOR OR SOMETHING LIKE 

1274
01:04:22,205 --> 01:04:22,839
THAT.

1275
01:04:22,839 --> 01:04:25,408
BY THE WAY, SAMMY, HOW OLD ARE 

1276
01:04:25,408 --> 01:04:25,575
YOU?

1277
01:04:25,575 --> 01:04:34,417
>> I'M 28 NOW.

1278
01:04:34,417 --> 01:04:36,853
IT IS BEAUTIFUL BECAUSE I TELL A

1279
01:04:36,853 --> 01:04:42,959
PATIENT THERE'S A DRUG.

1280
01:04:42,959 --> 01:04:49,499
IT IS GREAT AND I WAS AMAZED 

1281
01:04:49,499 --> 01:04:52,902
WHEN YOU WERE TALKING, YOU, 

1282
01:04:52,902 --> 01:04:56,473
FRANCIS AND LESLIE HOW IT 

1283
01:04:56,473 --> 01:04:57,807
DEVELOPS AT THE BEGINNING.

1284
01:04:57,807 --> 01:05:01,311
IT WAS CRAZY BECAUSE IN SEVEN 

1285
01:05:01,311 --> 01:05:07,684
YEARS YOU WERE ABLE TO FIND THE 

1286
01:05:07,684 --> 01:05:09,586
MUTATION CREATE A MODEL AND FIND

1287
01:05:09,586 --> 01:05:10,720
THE DRUG AND DRIVE IT INTO THE 

1288
01:05:10,720 --> 01:05:13,556
CLINICAL TRIAL.

1289
01:05:13,556 --> 01:05:15,425
IT WAS AMAZING.

1290
01:05:15,425 --> 01:05:16,893
IT'S BEAUTIFUL FOR ME TO EXPLAIN

1291
01:05:16,893 --> 01:05:21,765
THIS TO THE OTHERS TO SAY AND 

1292
01:05:21,765 --> 01:05:23,333
THIS IS MY EXPERIENCE, I'M 28.

1293
01:05:23,333 --> 01:05:25,001
THE DRUG IS WORKING.

1294
01:05:25,001 --> 01:05:31,574
WE HAVE TO DO MORE.

1295
01:05:31,574 --> 01:05:33,410
>> THAT'S THE PERFECT SET
UP FOR

1296
01:05:33,410 --> 01:05:36,946
ME TO TELL YOU LIKE YOU SAID 

1297
01:05:36,946 --> 01:05:38,548
THIS IS A TREATMENT NOT A CURE 

1298
01:05:38,548 --> 01:05:43,253
AND AN ALWAYS TELL FAMILIES THE 

1299
01:05:43,253 --> 01:05:48,291
NUMBER ONE THING THAT THE 

1300
01:05:48,291 --> 01:05:49,859
CLINICAL TRIALS SHOWED US IS WE 

1301
01:05:49,859 --> 01:05:51,661
DISCOVERED SOMETHING WE NEVER 

1302
01:05:51,661 --> 01:05:51,995
KNEW.

1303
01:05:51,995 --> 01:05:54,664
WE CAN REVERSE SOME OF THIS 

1304
01:05:54,664 --> 01:05:55,598
DISEASE.

1305
01:05:55,598 --> 01:05:56,599
IT CAN BE DONE.

1306
01:05:56,599 --> 01:05:57,467
EVERYBODY BENEFITTED THE YOUNG 

1307
01:05:57,467 --> 01:06:07,977
AND OLDER KIDS DID, EVERYBODY.

1308
01:06:10,046 --> 01:06:13,183
IT'S SOMETHING WE CAN REVERSE 

1309
01:06:13,183 --> 01:06:17,987
AND BETTER TREATMENT AND CURE.

1310
01:06:17,987 --> 01:06:19,356
FRANCIS: WHERE ARE WE NOW?

1311
01:06:19,356 --> 01:06:21,758
IT'S A TREATMENT NOT A CURE.

1312
01:06:21,758 --> 01:06:23,393
WE WERE ABLE TO BRING PEOPLE 

1313
01:06:23,393 --> 01:06:26,429
LIKE SAMMY INTO THEIR 20s WHICH 

1314
01:06:26,429 --> 01:06:28,965
WAS UNHEARD OF BEFORE AND TO 

1315
01:06:28,965 --> 01:06:31,501
STOP NOW WOULD MAKE NO SENSE 

1316
01:06:31,501 --> 01:06:32,335
WHEN WE'RE GETTING OPPORTUNITIES

1317
01:06:32,335 --> 01:06:33,636
COMING FROM NEW IDEAS IN SCIENCE

1318
01:06:33,636 --> 01:06:35,572
THAT CAN BE INVESTED IN.

1319
01:06:35,572 --> 01:06:37,607
I WANT TO TELL YOU ABOUT SOME OF

1320
01:06:37,607 --> 01:06:38,241
THE THINGS HAPPENING NOW WHICH 

1321
01:06:38,241 --> 01:06:40,944
IS VERY MUCH WORK IN PROGRESS.

1322
01:06:40,944 --> 01:06:42,879
WHICH WE ARE BOLD ENOUGH TO SAY 

1323
01:06:42,879 --> 01:06:45,915
MAY TAKE US TO THE NEXT LEVEL OF

1324
01:06:45,915 --> 01:06:47,050
INTERVENTIONS WITH THIS 

1325
01:06:47,050 --> 01:06:48,284
CONDITION MAYBE EVEN THAT CURE 

1326
01:06:48,284 --> 01:06:58,762
THAT WE ARE ALL DREAMING OF.

1327
01:06:59,396 --> 01:07:02,632
AND THREE CATEGORIES.

1328
01:07:02,632 --> 01:07:06,069
SMALL MOLECULE DRUGS THE 

1329
01:07:06,069 --> 01:07:09,906
TRANSFERASE INHIBITOR AND MTOR 

1330
01:07:09,906 --> 01:07:13,676
INHIBITORS BEING TESTED IN 

1331
01:07:13,676 --> 01:07:15,111
CLINICAL TRIAL IN BOSTON FOR THE

1332
01:07:15,111 --> 01:07:16,813
RESULTS ARE NOT YET CLEAR AND I 

1333
01:07:16,813 --> 01:07:19,516
WANT TO TALK ABOUT RNA AND DNA 

1334
01:07:19,516 --> 01:07:20,650
THERAPY BECAUSE AFTER ALL WE'RE 

1335
01:07:20,650 --> 01:07:25,922
TALKING ABOUT A DISEASE WHERE WE

1336
01:07:25,922 --> 01:07:29,459
KNOW WE KNOW THE NUCLEIC ACID 

1337
01:07:29,459 --> 01:07:29,893
INVOLVED.

1338
01:07:29,893 --> 01:07:31,995
THE C TO A T.

1339
01:07:31,995 --> 01:07:32,695
DOESN'T SOUND LIKE THAT 

1340
01:07:32,695 --> 01:07:33,763
SOMETHING YOU'D GO RIGHT TO 

1341
01:07:33,763 --> 01:07:35,265
WHERE THE ACTION IS TO GET THE 

1342
01:07:35,265 --> 01:07:36,099
BENEFIT AND THE RNA OR MAYBE THE

1343
01:07:36,099 --> 01:07:46,176
DNA.

1344
01:07:48,545 --> 01:07:51,581
WE LOOKED AT CELL CULTURE TO BE 

1345
01:07:51,581 --> 01:07:53,450
ABLE TO BLOCK THAT ABNORMAL 

1346
01:07:53,450 --> 01:07:54,083
SPLICE THAT CAUSES ALL THE 

1347
01:07:54,083 --> 01:08:00,390
TROUBLE.

1348
01:08:00,390 --> 01:08:08,264
A PMO WAS DESIGN IDEALLY SO IT 

1349
01:08:08,264 --> 01:08:12,202
WOULD SIT ON TOP OF THE MUTATION

1350
01:08:12,202 --> 01:08:13,970
PREVENTING THE SPLICE APPARATUS 

1351
01:08:13,970 --> 01:08:16,973
FROM RECOGNIZING IT AS A SPLICE 

1352
01:08:16,973 --> 01:08:18,241
DONOR SO SPLICING WOULD PROCEED 

1353
01:08:18,241 --> 01:08:19,309
THE WAY IT WAS SUPPOSED TO.

1354
01:08:19,309 --> 01:08:27,350
HOW'S THE DATA LOOK?

1355
01:08:27,350 --> 01:08:31,654
YOU CAN SEE WHAT WAS SYNTHESIZED

1356
01:08:31,654 --> 01:08:33,456
STEPPING ACROSS THE X IN THE 

1357
01:08:33,456 --> 01:08:36,059
MIDDLE AND DOWN BELOW YOU SEE 

1358
01:08:36,059 --> 01:08:37,894
THE DATA IN CULTURED CELLS WHAT 

1359
01:08:37,894 --> 01:08:40,797
HAPPENS WHEN YOU APPLY THESE 

1360
01:08:40,797 --> 01:08:42,699
PARTICULAR ONE TO THE PRODUCTION

1361
01:08:42,699 --> 01:08:47,437
OF LAMIN A PROGERIN THE P OR 

1362
01:08:47,437 --> 01:08:49,305
LAMBIN C THE DIFFERENT ISOFORM 

1363
01:08:49,305 --> 01:08:50,139
OF THE SAME GENE THAT STOPS 

1364
01:08:50,139 --> 01:08:52,375
UPSTREAM OF THE MUTATION SO IT'S

1365
01:08:52,375 --> 01:08:55,678
NOT AFFECTED IN PROGERIA AND YOU

1366
01:08:55,678 --> 01:08:57,914
CAN SEE THE HISTO GRAMS SHOWING 

1367
01:08:57,914 --> 01:09:01,150
THE RNA RESULTS BELOW AND THE 

1368
01:09:01,150 --> 01:09:01,851
WESTERN BLOT.

1369
01:09:01,851 --> 01:09:03,720
WE HADN'T SHOWN YOU BEFORE.

1370
01:09:03,720 --> 01:09:07,390
YOU CAN SEE PROGERIN ON A 

1371
01:09:07,390 --> 01:09:13,830
WESTERN BLOT THE MIDDLE BAND AND

1372
01:09:13,830 --> 01:09:16,833
THIS GIVES A STRONG RESPONSE IN 

1373
01:09:16,833 --> 01:09:20,270
TERMS OF KNOCKING WAY BACK ON 

1374
01:09:20,270 --> 01:09:22,605
PROGERIN AND KNOCKS DOWN LAMIN A

1375
01:09:22,605 --> 01:09:23,072
SIGNIFICANTLY.

1376
01:09:23,072 --> 01:09:25,542
WE DON'T THINK THAT'S PROBABLY 

1377
01:09:25,542 --> 01:09:26,175
DANGEROUS.

1378
01:09:26,175 --> 01:09:28,311
LAMIN C COMPENSATES BY GOING UP 

1379
01:09:28,311 --> 01:09:28,645
A BIT.

1380
01:09:28,645 --> 01:09:31,080
IF YOU HAD TO PICK ONE, I THINK 

1381
01:09:31,080 --> 01:09:34,517
YOU PICK ONE AND THAT'S CALLED 

1382
01:09:34,517 --> 01:09:35,418
SRP2001 AND WORKED WITH A 

1383
01:09:35,418 --> 01:09:37,520
COMPANY AT THE TIME HENCE THE 

1384
01:09:37,520 --> 01:09:47,597
SRP.

1385
01:09:58,341 --> 01:10:00,343
AND THERE'S A TWICE INTRAVENOUS 

1386
01:10:00,343 --> 01:10:02,712
INFUSION AND SEEING WHAT WOULD 

1387
01:10:02,712 --> 01:10:03,947
HAPPEN STARTING EARLY AND 

1388
01:10:03,947 --> 01:10:05,915
PROGRESSING DURING THE LIFE SPAN

1389
01:10:05,915 --> 01:10:07,750
AND YOU CAN SEE IT'S PRETTY 

1390
01:10:07,750 --> 01:10:08,051
IMPRESSIVE.

1391
01:10:08,051 --> 01:10:09,986
WE GOT CLEARLY A SIGNIFICANT 

1392
01:10:09,986 --> 01:10:12,188
EXTENSION OF LIFE AND JUST THE 

1393
01:10:12,188 --> 01:10:12,755
APPEARANCE OF THE ANIMAL IS 

1394
01:10:12,755 --> 01:10:18,695
BETTER.

1395
01:10:18,695 --> 01:10:20,663
WE COULD NEVER HAVE DONE THIS 

1396
01:10:20,663 --> 01:10:21,898
WITHOUT THE SUPERB MOUSE 

1397
01:10:21,898 --> 01:10:22,999
RESOURCE WE HAVE AT NIH.

1398
01:10:22,999 --> 01:10:27,804
I PARTICULARLY GOT A CALL OUT 

1399
01:10:27,804 --> 01:10:29,906
OUR LONG-TERM MOUSE EXPERT WHO 

1400
01:10:29,906 --> 01:10:32,275
MAKES ALL THESE THINGS POSSIBLE 

1401
01:10:32,275 --> 01:10:34,377
WITH VERY LARGE NUMBERS OF 

1402
01:10:34,377 --> 01:10:35,445
ANIMALS AND RIGOROUS RECORD 

1403
01:10:35,445 --> 01:10:37,547
KEEPING AND THE ABILITY TO DO 

1404
01:10:37,547 --> 01:10:39,549
TWICE WEEKLY INTRAVENOUS 

1405
01:10:39,549 --> 01:10:41,017
INFUSION OF THE SAME MOUSE FOR 

1406
01:10:41,017 --> 01:10:43,786
MANY WEEKS ON END AND NOT HAVE 

1407
01:10:43,786 --> 01:10:44,687
THAT BE A PROBLEM.

1408
01:10:44,687 --> 01:10:55,231
WE'RE FORTUNATE IN THAT REGARD.

1409
01:10:55,498 --> 01:10:57,533
THE HUMAN TRIAL IS THE 

1410
01:10:57,533 --> 01:10:59,202
CONVERSATION WE SPENT SOME OF 

1411
01:10:59,202 --> 01:11:02,138
OUR TIME THIS AFTERNOON TALKING 

1412
01:11:02,138 --> 01:11:02,405
ABOUT.

1413
01:11:02,405 --> 01:11:05,308
HOW DO YOU TAKE THIS FINDING TO 

1414
01:11:05,308 --> 01:11:08,711
A CLINICAL TRIAL.

1415
01:11:08,711 --> 01:11:13,016
THIS IS A PEPTIDE OLIGOMER AND 

1416
01:11:13,016 --> 01:11:17,920
THINK OF IT OF AN RNA BUT HAS A 

1417
01:11:17,920 --> 01:11:20,657
PEPTIDE ATTACHED MAKING IT MORE 

1418
01:11:20,657 --> 01:11:22,425
LIKELY TO GET INTO THE CELLS YOU

1419
01:11:22,425 --> 01:11:29,899
WANT AND A NAKED ONE WOULD 

1420
01:11:29,899 --> 01:11:31,534
MORPHOLINNO BECAUSE AWAY WANT 

1421
01:11:31,534 --> 01:11:33,936
THEM IN THE MUSCLE CELLS AND 

1422
01:11:33,936 --> 01:11:35,905
THAT WAS HAPPENING.

1423
01:11:35,905 --> 01:11:45,114
WHAT TO DO?

1424
01:11:45,114 --> 01:11:47,750
IT HAS TO SHIFT OVER TO A MEANS 

1425
01:11:47,750 --> 01:11:49,419
OF ADMINISTRATION THAT COULD BE 

1426
01:11:49,419 --> 01:11:52,088
PRACTICAL AND THAT MEANS SUB 

1427
01:11:52,088 --> 01:11:52,689
CUTANE

1428
01:11:52,689 --> 01:11:52,955
CUTANEOUS.

1429
01:11:52,955 --> 01:11:53,890
THIS HAS BEEN DONE.

1430
01:11:53,890 --> 01:11:55,925
LESLIE AND HER TEAM MANAGED TO 

1431
01:11:55,925 --> 01:11:58,494
DO THE FORMULATION AND DONE THE 

1432
01:11:58,494 --> 01:11:59,128
APPROPRIATE CHECKING TO MAKE 

1433
01:11:59,128 --> 01:12:00,296
SURE IT GETS IN THE SYSTEM IN 

1434
01:12:00,296 --> 01:12:01,097
THE RIGHT WAY.

1435
01:12:01,097 --> 01:12:03,933
NOW IT BECOMES MORE PRACTICAL TO

1436
01:12:03,933 --> 01:12:05,134
IMAGINE ADMINISTERING THIS NOT 

1437
01:12:05,134 --> 01:12:09,205
IN OUT OF THE WAY PLACES THAT 

1438
01:12:09,205 --> 01:12:10,907
PHARMACO DYNAMICS HAS ALSO BEEN 

1439
01:12:10,907 --> 01:12:11,240
DONE.

1440
01:12:11,240 --> 01:12:12,508
AGAIN, WE'RE TALKING ABOUT 

1441
01:12:12,508 --> 01:12:15,211
TAKING SOME OF THE FDA.

1442
01:12:15,211 --> 01:12:17,480
I WANTED TO BE PART OF THE 

1443
01:12:17,480 --> 01:12:19,716
DEMYSTIFYING MEDICINE TO BE MORE

1444
01:12:19,716 --> 01:12:20,817
EXPLICIT THAN WE SOMETIMES DO 

1445
01:12:20,817 --> 01:12:23,052
ABOUT HOW TO GO FROM AN ANIMAL 

1446
01:12:23,052 --> 01:12:24,821
MODEL RESULT TO A CLINICAL 

1447
01:12:24,821 --> 01:12:25,388
TRIAL.

1448
01:12:25,388 --> 01:12:26,055
HAVE YOU A LOT OF THINGS THAT 

1449
01:12:26,055 --> 01:12:29,892
HAVE TO BE DONE IN A RIGOROUS 

1450
01:12:29,892 --> 01:12:32,128
WAY OR THE FDA WILL SAY NOT YET,

1451
01:12:32,128 --> 01:12:33,730
GO BACK AND START OVER AND IT 

1452
01:12:33,730 --> 01:12:35,865
COSTS A LOT OF MONEY AND TIME 

1453
01:12:35,865 --> 01:12:38,234
AND YOU WANT TO DO IT EXACTLY 

1454
01:12:38,234 --> 01:12:38,901
RIGHT.

1455
01:12:38,901 --> 01:12:41,237
THERE NEEDS TO BE ANIMAL STUDIES

1456
01:12:41,237 --> 01:12:41,904
TO ASSESS TOXICITY.

1457
01:12:41,904 --> 01:12:43,139
THERE'S ALREADY BEEN SOME OF 

1458
01:12:43,139 --> 01:12:47,243
THAT ON OTHER PPMOs SOME OF 

1459
01:12:47,243 --> 01:12:48,511
WHICH HAVE GONE TO CLINICAL 

1460
01:12:48,511 --> 01:12:48,911
TRIALS.

1461
01:12:48,911 --> 01:12:50,480
YOU HAVE TO FIGURE OUT WHAT'S 

1462
01:12:50,480 --> 01:12:52,215
THE RIGHT DOSE AND WHAT'S THE 

1463
01:12:52,215 --> 01:12:54,484
TOP DOSE YOU COULD GO TO AND NOT

1464
01:12:54,484 --> 01:12:56,552
START TO GET INTO TOXICITY AND 

1465
01:12:56,552 --> 01:12:57,854
WHAT IS GOING TO BE THE WAY IN 

1466
01:12:57,854 --> 01:12:58,387
WHICH YOU DECIDE IF IT'S 

1467
01:12:58,387 --> 01:13:08,531
WORKING?

1468
01:13:15,238 --> 01:13:17,774
WE NEED A BIOMARKER.

1469
01:13:17,774 --> 01:13:19,776
YOU'LL HEAR ABOUT ONE FROM 

1470
01:13:19,776 --> 01:13:20,543
LESLIE.

1471
01:13:20,543 --> 01:13:22,879
YOU HEARD ABOUT PULSE WAVE 

1472
01:13:22,879 --> 01:13:23,713
VELOCITY AND DIAGNOSTIC 

1473
01:13:23,713 --> 01:13:25,314
FUNCTION.

1474
01:13:25,314 --> 01:13:27,250
YOU HAVEN'T HEARD ABOUT THE 

1475
01:13:27,250 --> 01:13:29,986
CARDIAC SIDE OF PROGERIA AND 

1476
01:13:29,986 --> 01:13:33,122
THERE'LL BE MEASURABLE 

1477
01:13:33,122 --> 01:13:34,323
PHYSIOLOGIC CHANGE YOU COULD 

1478
01:13:34,323 --> 01:13:35,057
ASSESS AND THERE'S 

1479
01:13:35,057 --> 01:13:35,391
MANUFACTURING.

1480
01:13:35,391 --> 01:13:45,802
WHO WILL MAKE THE DRUG.

1481
01:13:49,172 --> 01:13:51,174
AND YOU GET ATTENTION AND THIS 

1482
01:13:51,174 --> 01:13:53,676
IS NITTY-GRITTY STUFF AND MOST 

1483
01:13:53,676 --> 01:13:54,377
ACADEMICS DO NOT HAVE THAT 

1484
01:13:54,377 --> 01:13:56,078
EXPERIENCE, I CAN TELL YOU.

1485
01:13:56,078 --> 01:13:59,982
YOU NEED OTHER EXPERTS TO FIND 

1486
01:13:59,982 --> 01:14:02,451
YOUR WAY INTO THAT YOU CAN MAKE 

1487
01:14:02,451 --> 01:14:03,953
YOUR APPLICATION AND SAY I WANT 

1488
01:14:03,953 --> 01:14:05,721
TO START A FIRST IN HUMAN TRIAL 

1489
01:14:05,721 --> 01:14:07,023
AND THEY'LL TELL YOU YES OR NO 

1490
01:14:07,023 --> 01:14:09,892
AND COME BACK WITH MORE DATA 

1491
01:14:09,892 --> 01:14:16,866
LATER WHICH IS ALWAYS A CONCERN.

1492
01:14:16,866 --> 01:14:19,869
THAT'S WHERE WE ARE AND AT THE 

1493
01:14:19,869 --> 01:14:21,337
SAME TIME LET'S TRY EVERYTHING 

1494
01:14:21,337 --> 01:14:23,573
WE THINK MIGHT WORK AND TRY TO 

1495
01:14:23,573 --> 01:14:25,541
FIX THAT MUTATION.

1496
01:14:25,541 --> 01:14:28,144
NOW, THIS IS CRAZY TO IMAGINE 

1497
01:14:28,144 --> 01:14:28,878
THE POSSIBILITY OF SOMETHING 

1498
01:14:28,878 --> 01:14:30,112
LIKE THAT.

1499
01:14:30,112 --> 01:14:31,981
IF YOU TOLD ME 10 OR 15 YEARS 

1500
01:14:31,981 --> 01:14:34,550
AGO WE'RE ALREADY WORKING ON 

1501
01:14:34,550 --> 01:14:36,319
PROGERIA YOU WILL BE IN ANOTHER 

1502
01:14:36,319 --> 01:14:37,954
DECADE OR SO DESIGNING A TRIAL 

1503
01:14:37,954 --> 01:14:42,859
THAT WILL ACTUALLY GO IN AND 

1504
01:14:42,859 --> 01:14:46,762
EDIT THAT MUTATION IN VIVO IN 

1505
01:14:46,762 --> 01:14:47,930
APPROPRIATE TISSUE I WOULD SAY 

1506
01:14:47,930 --> 01:14:51,133
THERE'S NO WAY THAT COULD HAPPEN

1507
01:14:51,133 --> 01:14:57,306
IN MY LIFE TIME OR ANYBODY EL

1508
01:14:57,306 --> 01:14:59,108
ELSE'S THAT'S WHAT HAPPENED.

1509
01:14:59,108 --> 01:14:59,876
CRISPR HAS THE OPPORTUNITY TO 

1510
01:14:59,876 --> 01:15:02,879
FIND AND REPLACE IN YOUR GENOME 

1511
01:15:02,879 --> 01:15:03,813
WORD DOCUMENT AND THAT'S 

1512
01:15:03,813 --> 01:15:05,915
BASICALLY WHAT WE ARE TRYING TO 

1513
01:15:05,915 --> 01:15:16,325
DO IN THE CIRCUMSTANCE.

1514
01:15:16,325 --> 01:15:17,460
YOU'RE KNOCKING SOMETHING OUT 

1515
01:15:17,460 --> 01:15:18,494
AND DOING A DOUBLE STRANDED 

1516
01:15:18,494 --> 01:15:18,961
BREAK.

1517
01:15:18,961 --> 01:15:21,030
THAT'S NOT WHAT WE WANT TO DO 

1518
01:15:21,030 --> 01:15:21,230
HERE.

1519
01:15:21,230 --> 01:15:24,934
YOU HAVE A TOXIC PROTEIN THAT 

1520
01:15:24,934 --> 01:15:26,769
HAS A C TO A T YOU WANT TO 

1521
01:15:26,769 --> 01:15:29,772
CONVERT THAT T BACK TO A C OR 

1522
01:15:29,772 --> 01:15:31,207
THINK ABOUT IT ON THE OTHER 

1523
01:15:31,207 --> 01:15:33,042
STRAND CONVERT AN A TO A G.

1524
01:15:33,042 --> 01:15:34,810
WHAT YOU DO NEED TO DO THAT?

1525
01:15:34,810 --> 01:15:44,320
YOU NEED A DEOXYADENOSINE 

1526
01:15:44,320 --> 01:15:45,821
DEAMYLASE AND THIS IS WHERE 

1527
01:15:45,821 --> 01:15:47,890
WE'VE HAD GOOD FORTUNE IN A 

1528
01:15:47,890 --> 01:15:51,594
RELATIONSHIP THAT BEGAN IN THE 

1529
01:15:51,594 --> 01:15:52,628
CLINICAL CENTER WHEN DAVID LU 

1530
01:15:52,628 --> 01:15:54,463
CAME TO GIVE A TALK AS PART OF 

1531
01:15:54,463 --> 01:15:57,099
THE WEDNESDAY AFTERNOON LECTURE 

1532
01:15:57,099 --> 01:16:02,605
AND TOLD ME HE'D BEEN WORK A 

1533
01:16:02,605 --> 01:16:12,848
LITTLE BIT ON PROGER YA AND BY 

1534
01:16:12,848 --> 01:16:15,551
THE END OF THE AFTERNOON WE 

1535
01:16:15,551 --> 01:16:16,986
STARTED A COLLABORATION WHICH 

1536
01:16:16,986 --> 01:16:24,593
CONTINUES TO THIS DAY.

1537
01:16:24,593 --> 01:16:25,561
THIS IS THE APPROPRIATE GENE 

1538
01:16:25,561 --> 01:16:35,438
EDITOR.

1539
01:16:35,438 --> 01:16:38,507
WE FIGURED THE SYSTEM IS AAV AND

1540
01:16:38,507 --> 01:16:43,446
AAV9 A PARTICULAR VERSION OF 

1541
01:16:43,446 --> 01:16:45,815
THAT VIRUS AV9 HAS A PACKAGING 

1542
01:16:45,815 --> 01:16:47,249
LIMIT AND WHEN YOU TRY TO FIGURE

1543
01:16:47,249 --> 01:16:49,051
OUT HOW YOU'RE GOING TO PUT INTO

1544
01:16:49,051 --> 01:16:53,122
THAT VIRUS ALL THE APPARATUS YOU

1545
01:16:53,122 --> 01:16:58,761
NEED TO DO THIS SPECIFIC 

1546
01:16:58,761 --> 01:17:02,798
ADENOSINE EDIT AND NEED THAT 

1547
01:17:02,798 --> 01:17:08,104
COMPLICATED SET OF SKIGGSQUIGGLD

1548
01:17:08,104 --> 01:17:09,638
MOLECULES AND INSTEAD THEY CAME 

1549
01:17:09,638 --> 01:17:11,707
UP WITH THIS CLEVER APPROACH OF 

1550
01:17:11,707 --> 01:17:13,542
HAVING TWO SEPARATE AAVs.

1551
01:17:13,542 --> 01:17:17,213
EACH OF WHICH HAS PART OF WHAT 

1552
01:17:17,213 --> 01:17:18,814
YOU NEED BUT DESIGNED IF THEY 

1553
01:17:18,814 --> 01:17:21,884
GET IN THE SAME CELL THE WHOLE 

1554
01:17:21,884 --> 01:17:24,186
THING ASSEMBLES ITSELF PROPERLY.

1555
01:17:24,186 --> 01:17:33,162
I THOUGHT THIS WAS AWFULLY LIKE 

1556
01:17:33,162 --> 01:17:35,331
YOU HAVE TO GET THE SAME CELL 

1557
01:17:35,331 --> 01:17:37,566
INFECTED BY TWO VIRUSES AND LOOK

1558
01:17:37,566 --> 01:17:47,810
WHAT HAPPENED.

1559
01:17:49,245 --> 01:17:51,747
THIS IS MICE INJECTED 

1560
01:17:51,747 --> 01:17:53,716
INTRAVENOUSLY WITH THE DOUBLE 

1561
01:17:53,716 --> 01:17:56,085
AAV CONSTRUCT AND THEN LOOKING 

1562
01:17:56,085 --> 01:17:59,855
TO SEE WHAT HAPPENS AT SIX WEEKS

1563
01:17:59,855 --> 01:18:02,825
OR AT SIX MONTHS IN TERMS OF 

1564
01:18:02,825 --> 01:18:04,794
CORRECTING THE SINGLE NUCLEOTIDE

1565
01:18:04,794 --> 01:18:05,895
CHANGE.

1566
01:18:05,895 --> 01:18:09,231
HARVEST TISSUES, DO THE PCR AND 

1567
01:18:09,231 --> 01:18:10,266
SEQUENCE WHAT'S THERE.

1568
01:18:10,266 --> 01:18:12,968
THE LIVER ALWAYS GETS THE BEST 

1569
01:18:12,968 --> 01:18:15,438
RESULT BECAUSE LIVER LOVE 

1570
01:18:15,438 --> 01:18:17,606
ANYTHING YOU INJECT 

1571
01:18:17,606 --> 01:18:19,275
INTRAVENOUSLY SOMETHING LIKE 60%

1572
01:18:19,275 --> 01:18:19,875
OF THE CORRECTION HAPPENED.

1573
01:18:19,875 --> 01:18:21,911
EVEN IN PLACES WE CARE A LOT 

1574
01:18:21,911 --> 01:18:24,180
ABOUT, THE HEART AND THE AORTA, 

1575
01:18:24,180 --> 01:18:26,682
YOU'RE UP IN THE RANGE OF ABOUT 

1576
01:18:26,682 --> 01:18:28,951
20% WHICH IS PRETTY GOOD, PRETTY

1577
01:18:28,951 --> 01:18:30,152
AMAZING FOR A SINGLE INJECTION 

1578
01:18:30,152 --> 01:18:31,554
OF A VIRUS.

1579
01:18:31,554 --> 01:18:33,689
SO WE'RE PRETTY EXCITED.

1580
01:18:33,689 --> 01:18:35,658
THIS GETS US TO A PAPER IN 

1581
01:18:35,658 --> 01:18:38,060
NATURE AND THAT'S THREE YEARS 

1582
01:18:38,060 --> 01:18:38,494
AGO.

1583
01:18:38,494 --> 01:18:40,930
THERE'S A LOT OF WORK YET TO DO 

1584
01:18:40,930 --> 01:18:41,964
THOUGH IT FELT LIKE OKAY, LET'S 

1585
01:18:41,964 --> 01:18:46,335
TO PATIENTS NEXT.

1586
01:18:46,335 --> 01:18:48,838
THE CORRECTION OF THIS ALSO 

1587
01:18:48,838 --> 01:18:49,605
RESULTED IN SUBSTANTIAL 

1588
01:18:49,605 --> 01:18:50,072
LONGEVITY.

1589
01:18:50,072 --> 01:18:51,674
THAT WAS MORE EXCITING.

1590
01:18:51,674 --> 01:18:53,776
AGAIN ON THE LEFT YOU CAN SEE 

1591
01:18:53,776 --> 01:18:55,044
THE SAME KIND OF RESULTS ABOUT 

1592
01:18:55,044 --> 01:18:56,579
THE PERCENT OF CORRECTION.

1593
01:18:56,579 --> 01:18:58,914
YOU CAN SEE THE WESTERN BLOT 

1594
01:18:58,914 --> 01:19:00,216
SHOWING WHAT'S HAPPENED AND THE 

1595
01:19:00,216 --> 01:19:05,888
AORTA IN TERMS OF THAT PROGERIN 

1596
01:19:05,888 --> 01:19:16,332
WHICH IS LIKE GONE ALMOST.

1597
01:19:16,565 --> 01:19:17,800
AND SOME MICE LIVING TO THE SORT

1598
01:19:17,800 --> 01:19:21,036
OF NORMAL AGE RANGE AND SORRY 

1599
01:19:21,036 --> 01:19:22,671
THE VIDEOS DON'T WORK BECAUSE IF

1600
01:19:22,671 --> 01:19:25,541
I COULD RUN THEM YOU'D SEE THE 

1601
01:19:25,541 --> 01:19:26,575
UNTREATED CONTROL MOUSE IS 

1602
01:19:26,575 --> 01:19:27,676
LOOKING VERY SICK AND NOT MOVING

1603
01:19:27,676 --> 01:19:29,145
AROUND AND THE TREATED MICE ARE 

1604
01:19:29,145 --> 01:19:31,680
RUNNING AROUND HAVING A GOOD 

1605
01:19:31,680 --> 01:19:32,214
TIME.

1606
01:19:32,214 --> 01:19:33,616
AGAIN, DRAMATIC RESULT FROM A 

1607
01:19:33,616 --> 01:19:35,084
SINGLE INJECTION.

1608
01:19:35,084 --> 01:19:37,753
ONE THING THAT HELPED US HERE IS

1609
01:19:37,753 --> 01:19:39,054
THINK ABOUT WHAT'S HAPPENING IF 

1610
01:19:39,054 --> 01:19:42,091
YOU HAVE NOT CORRECTED ALL THE 

1611
01:19:42,091 --> 01:19:44,627
CELLS IN THE AORTA OF THE HEART 

1612
01:19:44,627 --> 01:19:46,929
THE ONCE YOU DIDN'T CORRECT WILL

1613
01:19:46,929 --> 01:19:49,331
SENESCE AND THEY'RE FADING AWAY.

1614
01:19:49,331 --> 01:19:51,700
THE ONES YOU DIDN'T CORRECT ARE 

1615
01:19:51,700 --> 01:19:53,936
FINE AND IF THEY HAVE MORE 

1616
01:19:53,936 --> 01:19:55,704
REPLICATIVE CAST HAVE YOU THIS 

1617
01:19:55,704 --> 01:19:57,139
IN VIVO SELECTION WORKING FOR 

1618
01:19:57,139 --> 01:19:58,807
YOU SO YOU DON'T HAVE TO HEAL 

1619
01:19:58,807 --> 01:20:01,577
100% IN THIS SITUATION TO GET A 

1620
01:20:01,577 --> 01:20:06,916
STRONG RESULT.

1621
01:20:06,916 --> 01:20:09,618
IN FACT WHEN WE LOOK 

1622
01:20:09,618 --> 01:20:10,386
MICROSCOPICALLY OF THOSE ANIMALS

1623
01:20:10,386 --> 01:20:12,488
IT LOOKS LIKE IT'S HARD TO FIND 

1624
01:20:12,488 --> 01:20:16,192
A CELL IN THE VASCULAR SMOOTH 

1625
01:20:16,192 --> 01:20:21,063
MUSCLE COMPARTMENT MAKING 

1626
01:20:21,063 --> 01:20:21,597
PROGE

1627
01:20:21,597 --> 01:20:21,864
PROGERIN.

1628
01:20:21,864 --> 01:20:23,566
THIS GOT PUT OUT AS AN EXAMPLE 

1629
01:20:23,566 --> 01:20:29,905
OF SOMETHING THAT MIGHT PARTLY 

1630
01:20:29,905 --> 01:20:32,041
LY -- POTENTIALLY TRANSLATABLE 

1631
01:20:32,041 --> 01:20:35,544
INTO A HUMAN TRIAL BUT LOTS OF 

1632
01:20:35,544 --> 01:20:37,513
THINGS TO THINK ABOUT.

1633
01:20:37,513 --> 01:20:38,547
WHERE ARE WE WITH THIS?

1634
01:20:38,547 --> 01:20:40,849
THERE'S AN ISSUE WITH THE DOUBLE

1635
01:20:40,849 --> 01:20:41,684
AAV PLAN.

1636
01:20:41,684 --> 01:20:43,552
IN ORDER TO GET HIGH ENOUGH 

1637
01:20:43,552 --> 01:20:44,920
EFFICIENCY OF GETTING BOTH 

1638
01:20:44,920 --> 01:20:46,355
VECTORS INTO THE SAME CELL YOU 

1639
01:20:46,355 --> 01:20:48,324
HAVE TO GIVE A HEAVY LOAD OF 

1640
01:20:48,324 --> 01:20:51,493
VIRUS AND WE KNOW FROM OTHER 

1641
01:20:51,493 --> 01:20:55,998
HUMAN TRIALS WITH AAV9 OR OTHERS

1642
01:20:55,998 --> 01:21:00,736
THERE'S RISK OF TOXICITY IF YOU 

1643
01:21:00,736 --> 01:21:05,741
GO FIVE TIMES 10 TO THE 15th 

1644
01:21:05,741 --> 01:21:06,976
VIRAL KILOGRAMS TROUBLE STARTS 

1645
01:21:06,976 --> 01:21:09,345
TO HAPPEN AND IF YOU'D LIKE TO 

1646
01:21:09,345 --> 01:21:13,182
LIMIT THAT YOU WANT THE SINGLE 

1647
01:21:13,182 --> 01:21:14,283
VECTOR AND NOT THE DOUBLE 

1648
01:21:14,283 --> 01:21:16,018
BECAUSE YOU OUT TO BE ABLE TO 

1649
01:21:16,018 --> 01:21:18,754
GET AWAY WITH THE LOWER DOSE.

1650
01:21:18,754 --> 01:21:20,155
THAT'S ONE THING.

1651
01:21:20,155 --> 01:21:24,293
COME BACK TO THAT IN A SECOND.

1652
01:21:24,293 --> 01:21:25,427
OTHER, YOU HAVE TO DO IT ALMOST 

1653
01:21:25,427 --> 01:21:27,296
AT BIRTH TO GET A POSITIVE 

1654
01:21:27,296 --> 01:21:27,663
RESULT.

1655
01:21:27,663 --> 01:21:30,299
WHAT IF YOU WAIT UNTIL THE MICE 

1656
01:21:30,299 --> 01:21:31,233
GET A LITTLE BIT SICK?

1657
01:21:31,233 --> 01:21:33,469
COULD YOU IN FACT EXTEND THEIR 

1658
01:21:33,469 --> 01:21:34,837
SURVIVAL AND SHOW BENEFIT?

1659
01:21:34,837 --> 01:21:35,838
WE'VE DONE AN EXPERIMENT WHICH 

1660
01:21:35,838 --> 01:21:37,906
IS STILL IN THE WORKS OF BEING 

1661
01:21:37,906 --> 01:21:41,277
ANALYZED AND WAITING UNTIL FOUR 

1662
01:21:41,277 --> 01:21:42,211
MONTHS AT WHICH TIME THESE MICE 

1663
01:21:42,211 --> 01:21:43,612
ARE PRETTY SICK AND INJECTED 

1664
01:21:43,612 --> 01:21:45,314
THEM AND I THINK IT'S PRETTY 

1665
01:21:45,314 --> 01:21:46,782
CLEAR THE CORRECTION STILL WORKS

1666
01:21:46,782 --> 01:21:47,683
PRETTY WELL.

1667
01:21:47,683 --> 01:21:49,818
THE RNA STILL WORKS PRETTY WELL.

1668
01:21:49,818 --> 01:22:00,362
WE'RE STILL DOING THE PATHOLOGY.

1669
01:22:08,604 --> 01:22:13,208
AND WE'VE HAD GREAT PARTNERS AND

1670
01:22:13,208 --> 01:22:16,712
IN MY LAB IN THE ROOM WE'VE 

1671
01:22:16,712 --> 01:22:19,548
WORKED TIRELESSLY ON THIS AND 

1672
01:22:19,548 --> 01:22:21,050
OTHER PROGERIA EFFORT.

1673
01:22:21,050 --> 01:22:24,320
THEY HAVE FIGURED OUT BY PICKING

1674
01:22:24,320 --> 01:22:27,089
THE RIGHT KAS 9 MORE CONSTRAINED

1675
01:22:27,089 --> 01:22:29,558
IN SIZE AND REENGINEERING THE 

1676
01:22:29,558 --> 01:22:33,228
EDIT BASE EDITOR SO IT'S NOT SO 

1677
01:22:33,228 --> 01:22:35,497
BULKY YOU CAN SQUEEZE THIS INTO 

1678
01:22:35,497 --> 01:22:38,400
A SINGLE AAV AND THEY HAVE NOW 

1679
01:22:38,400 --> 01:22:40,536
SENT THREE VERSIONS WITH THREE 

1680
01:22:40,536 --> 01:22:43,339
GUIDE RNAs AND IN RECENT DATA IT

1681
01:22:43,339 --> 01:22:44,606
LOOKS AS IF THOSE WORK JUST 

1682
01:22:44,606 --> 01:22:46,508
ABOUT AS EFFICIENTLY AS THE 

1683
01:22:46,508 --> 01:22:48,744
DOUBLE AAV WHICH IS VERY 

1684
01:22:48,744 --> 01:22:49,011
EXCITING.

1685
01:22:49,011 --> 01:22:50,212
SO I THINK IF WE'RE TALKING 

1686
01:22:50,212 --> 01:22:53,515
ABOUT NOW GOING FORWARD TO HUMAN

1687
01:22:53,515 --> 01:22:55,551
TRIAL WE MAY HAVE OUR DRUG AND 

1688
01:22:55,551 --> 01:22:56,685
DIDN'T UNTIL WE GOT TO THIS 

1689
01:22:56,685 --> 01:22:56,885
POINT.

1690
01:22:56,885 --> 01:22:59,455
WE STILL NEED TO GO BACK IN WITH

1691
01:22:59,455 --> 01:23:01,223
THE SINGLE VECTOR AND MAKE SURE 

1692
01:23:01,223 --> 01:23:05,427
IT REALLY WORKS LIKE THE DOUBLE 

1693
01:23:05,427 --> 01:23:07,930
DID WE ALSO ARE STICKING WITH 

1694
01:23:07,930 --> 01:23:10,366
AAV9 BECAUSE IT SEEMS TO HAVE 

1695
01:23:10,366 --> 01:23:12,601
THE RIGHT PROPERTIES BUT NOT 

1696
01:23:12,601 --> 01:23:12,868
IDEAL.

1697
01:23:12,868 --> 01:23:14,970
THERE'S A WHOLE WORLD OF NEW 

1698
01:23:14,970 --> 01:23:16,372
CAPSIDS OUT THERE TRYING TO 

1699
01:23:16,372 --> 01:23:17,840
FIGURE OUT WHETHER THERE'S 

1700
01:23:17,840 --> 01:23:19,341
SOMETHING BETTER AND SOMETHING 

1701
01:23:19,341 --> 01:23:20,676
THAT WOULDN'T COST US FIVE YEARS

1702
01:23:20,676 --> 01:23:22,378
IN TERMS OF GETTING IT THROUGH 

1703
01:23:22,378 --> 01:23:23,512
THE FDA.

1704
01:23:23,512 --> 01:23:25,547
THIS ALREADY MADE IT THROUGH THE

1705
01:23:25,547 --> 01:23:26,348
REGULATORY PROCESS.

1706
01:23:26,348 --> 01:23:29,218
JUST LIKE WITH THE RNA AND DOSE 

1707
01:23:29,218 --> 01:23:30,552
DETERMINATION AND TOX STUDIES, 

1708
01:23:30,552 --> 01:23:31,687
AND WE HAVE TO FIGURE OUT WHAT'S

1709
01:23:31,687 --> 01:23:36,125
GOING TO BE THE RILE END POINT 

1710
01:23:36,125 --> 01:23:38,093
IT BETTER NOT BE LONGEVITY AND 

1711
01:23:38,093 --> 01:23:40,596
QUICKER AND THE FDA APPLICATION.

1712
01:23:40,596 --> 01:23:42,531
WE HAVE TWO TRIALS COMPETING 

1713
01:23:42,531 --> 01:23:44,733
WITH EACH OTHER SIDE BY SIDE FOR

1714
01:23:44,733 --> 01:23:47,770
A RARE DISEASE AND SOME PEOPLE 

1715
01:23:47,770 --> 01:23:49,972
MAY SAY AREN'T YOU OVERDOING IT?

1716
01:23:49,972 --> 01:23:51,607
NO, I THINK WE WANT TO MAKE SURE

1717
01:23:51,607 --> 01:23:52,875
WE SOMEWHERE SOMETHING THAT 

1718
01:23:52,875 --> 01:23:54,843
WORKS AND BOTH HAVE POTENTIAL 

1719
01:23:54,843 --> 01:23:57,746
AND BOTH CAN RUN INTO SOMETHING 

1720
01:23:57,746 --> 01:23:59,348
UNEXPECTED THAT COULD SET US 

1721
01:23:59,348 --> 01:23:59,615
BACK.

1722
01:23:59,615 --> 01:24:01,383
THAT'S WHERE I WANTED TO TAKE IT

1723
01:24:01,383 --> 01:24:11,727
AND BACK TO LESLIE.

1724
01:24:16,598 --> 01:24:17,900
LESLIE: WE DON'T SEE IT UNTIL 

1725
01:24:17,900 --> 01:24:19,902
IT'S ALL CONCENTRATED IN THE ONE

1726
01:24:19,902 --> 01:24:20,369
TALK.

1727
01:24:20,369 --> 01:24:27,042
AS FRANCIS SAID IT TOOK US LIKE 

1728
01:24:27,042 --> 01:24:37,453
10 YEARS OF CONTINUOUS 

1729
01:24:39,388 --> 01:24:40,956
LONAFARNIB AND WE HAVE 

1730
01:24:40,956 --> 01:24:41,223
POTENTIAL.

1731
01:24:41,223 --> 01:24:45,494
IF YOU LOOK AT THE GRAPH BEING 

1732
01:24:45,494 --> 01:24:46,862
HERE'S LONAFARNIB EXTENDING IT 

1733
01:24:46,862 --> 01:24:51,934
25% AND THAT TRANSLATED INTO THE

1734
01:24:51,934 --> 01:24:52,134
HUMAN.

1735
01:24:52,134 --> 01:24:53,802
HERE'S THE SMALL MOLECULE AND 

1736
01:24:53,802 --> 01:24:55,404
THE DNA AND THERE'S NO REASON TO

1737
01:24:55,404 --> 01:24:58,073
THINK THIS COULDN'T HAPPEN IN A 

1738
01:24:58,073 --> 01:24:58,841
HUMAN AS WELL.

1739
01:24:58,841 --> 01:25:06,315
THE MICE LIVED INTO OLD AGE.

1740
01:25:06,315 --> 01:25:08,484
PEOPLE SAY OH, THAT'S A MOUSE.

1741
01:25:08,484 --> 01:25:10,052
HOW DO YOU LEAP FROM A MOUSE TO 

1742
01:25:10,052 --> 01:25:10,252
HUMAN.

1743
01:25:10,252 --> 01:25:12,621
WE DIT HERE AND HOW DO YOU DO IT

1744
01:25:12,621 --> 01:25:14,523
IN THE FUTURE AND IT TAKES 

1745
01:25:14,523 --> 01:25:14,756
TRYING.

1746
01:25:14,756 --> 01:25:17,092
WHAT ARE WE GOING TRY IN THE 

1747
01:25:17,092 --> 01:25:18,627
CLINICAL TRIAL AS AN EFFICACY 

1748
01:25:18,627 --> 01:25:19,561
OUTCOME?

1749
01:25:19,561 --> 01:25:21,363
YOU HAVE TO KNOW IF THE DRUG 

1750
01:25:21,363 --> 01:25:23,332
WORKS AND IF IT DOESN'T YOU HAVE

1751
01:25:23,332 --> 01:25:24,967
TO KNOW THAT TOO AND AS FAST AS 

1752
01:25:24,967 --> 01:25:26,568
POSSIBLE BECAUSE I WANT TO GET 

1753
01:25:26,568 --> 01:25:27,469
TO THE NEXT THING BECAUSE 

1754
01:25:27,469 --> 01:25:28,136
TOXICITY IS THERE.

1755
01:25:28,136 --> 01:25:29,404
YOU DON'T WANT TO DO A DRUG 

1756
01:25:29,404 --> 01:25:39,748
TRIAL FOR TOO LONG.

1757
01:25:40,115 --> 01:25:41,683
YOU WANT TO EVALUATE AND MOST 

1758
01:25:41,683 --> 01:25:45,888
WILL BE FIRST IN HUMAN AND THE 

1759
01:25:45,888 --> 01:25:49,458
CHALLENGES TO GET GREATER WITH 

1760
01:25:49,458 --> 01:25:51,126
ALL THIS LONG LIST OF THINGS 

1761
01:25:51,126 --> 01:25:52,628
FRANCIS HAS BEEN TALKING ABOUT.

1762
01:25:52,628 --> 01:25:54,696
IT'S QUITE AN ADVENTURE.

1763
01:25:54,696 --> 01:26:02,838
PUT IT THAT WAY.

1764
01:26:02,838 --> 01:26:05,607
WE'VE DEVELOPED A BIOMARKER.

1765
01:26:05,607 --> 01:26:07,342
WE DISCOVERED, LOOKED AND 

1766
01:26:07,342 --> 01:26:07,943
DISCOVERED PROGERIN IS IN THE 

1767
01:26:07,943 --> 01:26:09,778
BLOOD.

1768
01:26:09,778 --> 01:26:15,450
IT'S IN THE PLASMA AND DEVELOPED

1769
01:26:15,450 --> 01:26:22,791
A BIOMARKER AN OUTCOME MEASURE 

1770
01:26:22,791 --> 01:26:24,826
AND LOOKED AT CHILDREN WITH THIS

1771
01:26:24,826 --> 01:26:26,361
IN THE LOG SCALE AND THE REST OF

1772
01:26:26,361 --> 01:26:26,795
US.

1773
01:26:26,795 --> 01:26:30,165
LOW HERE AND HIGH HERE.

1774
01:26:30,165 --> 01:26:31,400
WE HAVE SOMETHING HIGH 

1775
01:26:31,400 --> 01:26:33,235
QUANTITATIVE AND IF WE LOOK DOWN

1776
01:26:33,235 --> 01:26:38,774
HERE, THIS BAR IS SHOWING YOU 

1777
01:26:38,774 --> 01:26:43,178
THERAPY AND ALL THE BARS OVER 10

1778
01:26:43,178 --> 01:26:45,414
YEARS, THIS IS SHOWING 

1779
01:26:45,414 --> 01:26:46,315
LONAFARNIB THERAPY.

1780
01:26:46,315 --> 01:26:48,517
YOU HAVE A DIP TO ABOUT HALF AND

1781
01:26:48,517 --> 01:26:50,419
THEN PRETTY MUCH A STEADY STATE.

1782
01:26:50,419 --> 01:26:51,453
IT STAYS LOW AND THAT IS GOING 

1783
01:26:51,453 --> 01:26:54,656
TO BE REALLY IMPORTANT.

1784
01:26:54,656 --> 01:26:56,959
THIS WILL HELP ASSESS THE NEXT 

1785
01:26:56,959 --> 01:26:57,893
DRUG BECAUSE IF IT WAS GOING 

1786
01:26:57,893 --> 01:27:00,262
BACK UP WE'D HAVE A DIFFERENT 

1787
01:27:00,262 --> 01:27:01,029
SITUATION THAN HERE AT A STEADY 

1788
01:27:01,029 --> 01:27:10,806
STATE OF LOW.

1789
01:27:10,806 --> 01:27:12,841
WE SHOWED WHEN YOU LOOK AT 

1790
01:27:12,841 --> 01:27:15,210
LENGTH OF TREATMENT AND THE 

1791
01:27:15,210 --> 01:27:17,446
AMOUNT OF YOU DECREASE, THE GRAY

1792
01:27:17,446 --> 01:27:18,847
BAR SHOWS THE AVERAGE DECREASE 

1793
01:27:18,847 --> 01:27:21,883
IN THE CHILDREN IN THE TRIAL AND

1794
01:27:21,883 --> 01:27:32,260
YOUNG ADULTS OF 15,000  

1795
01:27:32,260 --> 01:27:33,395
PICOGRAMS PER MILL AND THE 

1796
01:27:33,395 --> 01:27:35,464
LONGER YOU GO AND THE LONGER YOU

1797
01:27:35,464 --> 01:27:38,066
STAY LOW THE GREATER THE 

1798
01:27:38,066 --> 01:27:38,500
BENEFIT.

1799
01:27:38,500 --> 01:27:40,402
THIS IS THE INCREASE IN LIFE 

1800
01:27:40,402 --> 01:27:40,702
EXPECTANCY.

1801
01:27:40,702 --> 01:27:42,738
LOOK AT THIS AFTER 10 YEARS, 

1802
01:27:42,738 --> 01:27:44,940
WHICH WE SURPASSED IN MANY KIDS,

1803
01:27:44,940 --> 01:27:46,141
WE'RE TALKING ABOUT ALMOST SEVEN

1804
01:27:46,141 --> 01:27:56,251
YEARS.

1805
01:28:08,764 --> 01:28:10,432
BACK TO YOU.

1806
01:28:10,432 --> 01:28:11,867
FRANCIS: BEFORE TELLING YOU THE 

1807
01:28:11,867 --> 01:28:13,301
WHOLE STORY AND YOU CAN SEE 

1808
01:28:13,301 --> 01:28:14,870
WE'RE ALL COMPELLED BY WHAT WE 

1809
01:28:14,870 --> 01:28:17,472
CAN STILL DO IN THE NEXT STEPS 

1810
01:28:17,472 --> 01:28:19,841
BUT ALSO THIS IS SUPPOSED TO BE 

1811
01:28:19,841 --> 01:28:21,677
REPRESENTED AS AN EXAMPLE OF 

1812
01:28:21,677 --> 01:28:23,378
SOMETHING THAT COULD BE 

1813
01:28:23,378 --> 01:28:25,580
HAPPENING FOR LOTS OF OTHER 

1814
01:28:25,580 --> 01:28:31,586
DISEASES.

1815
01:28:31,586 --> 01:28:32,921
THESE ARE THE DISORDERS FOR 

1816
01:28:32,921 --> 01:28:36,124
WHICH WE KNOW THE EXACT MUTATION

1817
01:28:36,124 --> 01:28:38,293
AND I NEED TO UPDATE THIS 

1818
01:28:38,293 --> 01:28:39,661
BECAUSE THIS IS THREE YEARS OUT 

1819
01:28:39,661 --> 01:28:41,396
OF DATE BUT THE BARS KEEP GOING 

1820
01:28:41,396 --> 01:28:42,564
UP.

1821
01:28:42,564 --> 01:28:47,002
IT'S ABOUT 7,000 CONDITIONS.

1822
01:28:47,002 --> 01:28:50,539
HOW MUCH WILL THOSE HAVE AN 

1823
01:28:50,539 --> 01:28:51,673
EFFECTIVE TREATMENT?

1824
01:28:51,673 --> 01:28:52,974
PROGERIA IS ONE BUT THERE'S AN 

1825
01:28:52,974 --> 01:28:56,778
AWFUL LOT OF THOSE STILL WAITING

1826
01:28:56,778 --> 01:29:01,850
EVEN THOUGH THEY HAVE FOR 

1827
01:29:01,850 --> 01:29:08,523
DIAGNOSTIC PURPOSES A LOT MORE 

1828
01:29:08,523 --> 01:29:08,724
KNOWN.

1829
01:29:08,724 --> 01:29:12,094
ONE REASON I'M EXCITED ABOUT 

1830
01:29:12,094 --> 01:29:14,229
PURSUING THIS IN GENE EDITING 

1831
01:29:14,229 --> 01:29:15,630
FOR PROGERIA BECAUSE IT FEELS 

1832
01:29:15,630 --> 01:29:17,032
LIKE THE KIND OF APPROACH THAT 

1833
01:29:17,032 --> 01:29:18,433
COULD BE SCALED TO LOTS OF 

1834
01:29:18,433 --> 01:29:19,301
DISEASES IF WE CAN FIGURE OUT 

1835
01:29:19,301 --> 01:29:21,303
HOW TO DO IT SAFELY AND 

1836
01:29:21,303 --> 01:29:21,603
EFFECTIVELY.

1837
01:29:21,603 --> 01:29:25,807
YOU NEED THE RIGHT EDITOR AND 

1838
01:29:25,807 --> 01:29:26,575
DELIVERY AND GOING TO THE TISSUE

1839
01:29:26,575 --> 01:29:28,110
AND ALL THAT NEEDS TO BE SAFE 

1840
01:29:28,110 --> 01:29:29,878
AND YOU CAN BEGIN TO SOMETHING 

1841
01:29:29,878 --> 01:29:32,781
GOING AFTER LOTS AND LOTS OF 

1842
01:29:32,781 --> 01:29:33,882
THESE CONDITIONS WITHOUT HAVING 

1843
01:29:33,882 --> 01:29:36,051
TO SPEND 10 OR 20 YEARS FIGURING

1844
01:29:36,051 --> 01:29:39,254
OUT THE PRECISE NATURE OF THEIR 

1845
01:29:39,254 --> 01:29:40,822
MOLECULAR BIOLOGY AND FIX THE 

1846
01:29:40,822 --> 01:29:41,089
MUTATION.

1847
01:29:41,089 --> 01:29:43,592
IT GETS HARDER WHEN YOU'RE 

1848
01:29:43,592 --> 01:29:44,426
TALKING ABOUT TISSUE TO BRAIN 

1849
01:29:44,426 --> 01:29:45,827
AND A LOT OF THESE ARE 

1850
01:29:45,827 --> 01:29:47,662
CONDITIONS FOR WHERE THE BRAIN 

1851
01:29:47,662 --> 01:29:52,234
IS INVOLVED BUT WE'RE STARTING 

1852
01:29:52,234 --> 01:29:55,170
TO SEE SUCCESSES WITH IN VIVO 

1853
01:29:55,170 --> 01:29:55,470
APPROACHES.

1854
01:29:55,470 --> 01:29:56,938
I GUESS WE OUGHT TO REFLECT AT 

1855
01:29:56,938 --> 01:30:00,842
THE END OF THIS PRESENTATION 

1856
01:30:00,842 --> 01:30:02,944
MORE BROADLY ABOUT WHAT THE 

1857
01:30:02,944 --> 01:30:04,646
LESSONS FROM PROGERIA MIGHT MEAN

1858
01:30:04,646 --> 01:30:05,447
FOR THESE OTHER CONDITIONS 

1859
01:30:05,447 --> 01:30:08,216
BECAUSE I THINK THERE'S BOTH 

1860
01:30:08,216 --> 01:30:10,352
ENORMOUS EXCITEMENT 

1861
01:30:10,352 --> 01:30:11,486
SCIENTIFICALLY AND ALSO A LOT OF

1862
01:30:11,486 --> 01:30:13,054
CONCERN HOW QUICKLY WE'LL BE 

1863
01:30:13,054 --> 01:30:17,826
ABLE TO GET THIS DONE BECAUSE 

1864
01:30:17,826 --> 01:30:20,762
WE'RE TALKING ABOUT ULTRA RARE 

1865
01:30:20,762 --> 01:30:21,429
DISEASES.

1866
01:30:21,429 --> 01:30:22,564
YOU WON'T SEE PHARMACEUTICAL 

1867
01:30:22,564 --> 01:30:24,366
COMPANIES SAYING I'LL SPEND $100

1868
01:30:24,366 --> 01:30:27,736
MILLION ON A CONDITION THAT ONLY

1869
01:30:27,736 --> 01:30:28,937
AFFECTS 30 PEOPLE.

1870
01:30:28,937 --> 01:30:31,406
WE HAVE AN ISSUE IN HOW TO SCALE

1871
01:30:31,406 --> 01:30:34,176
THIS IN A WAY THAT'S AFFORDABLE.

1872
01:30:34,176 --> 01:30:35,844
PRE CLINICAL AND CLINICAL COSTS 

1873
01:30:35,844 --> 01:30:40,515
AS WE'RE TRYING TO DO NOW AND 

1874
01:30:40,515 --> 01:30:43,885
TRYING TO FIGURE IT OUT HOW TO 

1875
01:30:43,885 --> 01:30:48,723
COBBLE IT TOGETHER WITH THE 

1876
01:30:48,723 --> 01:30:50,525
PROGERIA FOUNDATION AND ALL THE 

1877
01:30:50,525 --> 01:30:51,493
EFFORTS THAT HAVE REQUIRED 

1878
01:30:51,493 --> 01:30:54,796
SUPPORT WHERE DONORS HAD TO COME

1879
01:30:54,796 --> 01:30:54,963
UP.

1880
01:30:54,963 --> 01:30:56,198
THIS IS EXPENSIVE STUFF.

1881
01:30:56,198 --> 01:30:57,732
AND DO RUN ALL THE WAY FROM 

1882
01:30:57,732 --> 01:31:02,504
BEGINNING TO END WE'RE TALKING 

1883
01:31:02,504 --> 01:31:06,842
ABOUT TENS AND I THINK LESLIE 

1884
01:31:06,842 --> 01:31:11,680
SAID IT'S CLOSER TO 100 TO DO 

1885
01:31:11,680 --> 01:31:11,880
THIS.

1886
01:31:11,880 --> 01:31:13,481
WHERE'S IT ALL COME FROM IF THE 

1887
01:31:13,481 --> 01:31:14,883
TRIAL IS FOR A RARE DISEASE 

1888
01:31:14,883 --> 01:31:16,885
SEEKING TO ENROLL A SIGNIFICANT 

1889
01:31:16,885 --> 01:31:18,453
FRACTION OF THE PEOPLE WHO HAVE 

1890
01:31:18,453 --> 01:31:19,087
THE DISEASE.

1891
01:31:19,087 --> 01:31:20,121
SUPPOSE YOUR TRIAL WORKS AND YOU

1892
01:31:20,121 --> 01:31:30,665
CURE THEM ALL, WELL, THE MARKET 

1893
01:31:32,367 --> 01:31:36,171
JUST GOT SMALL BUT IN THE LAST 

1894
01:31:36,171 --> 01:31:46,715
TWO TO THREE YEARS AFTER INITIAL

1895
01:31:52,387 --> 01:31:55,557
ENTHUSIASM AND THERE'S DISEASES 

1896
01:31:55,557 --> 01:32:00,428
LIKE DUCHENNE'S AND THERE'S NOT 

1897
01:32:00,428 --> 01:32:02,430
A LOT OF INTEREST IN THE PRIVATE

1898
01:32:02,430 --> 01:32:03,965
SECTOR IN MAKING INVESTMENT.

1899
01:32:03,965 --> 01:32:05,233
SO WHAT DO WE DO?

1900
01:32:05,233 --> 01:32:08,436
OUR COLLEAGUES AT THE FDA ARE 

1901
01:32:08,436 --> 01:32:11,306
TRYING TO STEP BACK FROM 

1902
01:32:11,306 --> 01:32:12,240
UNNECESSARY LEVELS OF CONSTRAINT

1903
01:32:12,240 --> 01:32:16,978
ON HOW YOU CAN GET STARTED WITH 

1904
01:32:16,978 --> 01:32:18,446
THE TRIAL PARTICULARLY A BIG 

1905
01:32:18,446 --> 01:32:20,482
SHOUT OUT TO PETER MARKS AS A 

1906
01:32:20,482 --> 01:32:22,884
LEADER IN THAT SPACE AND COMING 

1907
01:32:22,884 --> 01:32:24,386
UP WITH WAYS MAYBE WITH 

1908
01:32:24,386 --> 01:32:25,287
TEMPLATES SO WHEN YOU BRING 

1909
01:32:25,287 --> 01:32:27,422
SOMETHING FORWARD IT'S NOT THE 

1910
01:32:27,422 --> 01:32:29,057
42 BOXES OF MATERIAL THAT IN THE

1911
01:32:29,057 --> 01:32:31,326
PAST OFTEN TIMES WERE NECESSARY 

1912
01:32:31,326 --> 01:32:31,893
BEFORE YOU COULD START THE 

1913
01:32:31,893 --> 01:32:37,666
CONVERSATION.

1914
01:32:37,666 --> 01:32:40,502
NIH IS THE BESPOKE CONSORTIUM 

1915
01:32:40,502 --> 01:32:42,337
AND THIS IS ONE OF THE 

1916
01:32:42,337 --> 01:32:44,739
ACCELERATING MEDICINES 

1917
01:32:44,739 --> 01:32:45,907
PARTNERSHIPS I HAD A CHANCE TO 

1918
01:32:45,907 --> 01:32:47,442
START A FEW YEARS AGO AND 

1919
01:32:47,442 --> 01:32:48,743
THEY'RE ALSO EXPLORING THE SAME 

1920
01:32:48,743 --> 01:32:51,012
WAYS OR WAY TO DO THIS AT LOWER 

1921
01:32:51,012 --> 01:32:53,114
COST AND MORE EFFICIENCY AND 

1922
01:32:53,114 --> 01:32:55,383
MAKING SOME PROGRESS BUT NOT TO 

1923
01:32:55,383 --> 01:32:58,620
THE POINT OF HAVING ANYWHERE 

1924
01:32:58,620 --> 01:33:00,655
NEAR SOLVE THE ISSUE.

1925
01:33:00,655 --> 01:33:01,556
PHILANTHROPY IS GOING TO BE 

1926
01:33:01,556 --> 01:33:02,958
CRITICAL BUT I DON'T THINK 

1927
01:33:02,958 --> 01:33:04,225
THERE'S ENOUGH FOR THESE 

1928
01:33:04,225 --> 01:33:05,560
DISEASES TO CALL THAT THE ANSWER

1929
01:33:05,560 --> 01:33:09,397
AND MAYBE THE NEW KID ON THE 

1930
01:33:09,397 --> 01:33:11,533
BLOCK ARPA-H WHICH WAS STARTED A

1931
01:33:11,533 --> 01:33:12,634
COUPLE YEARS AGO MAY SEE THIS AS

1932
01:33:12,634 --> 01:33:15,503
ONE OF THOSE GAME-CHANGING 

1933
01:33:15,503 --> 01:33:16,972
MOMENTS WHERE SOME INITIAL 

1934
01:33:16,972 --> 01:33:22,110
INVESTMENTS TO CREATE A PLATFORM

1935
01:33:22,110 --> 01:33:28,083
FOR THESE KINDS OF RARE DISEASE 

1936
01:33:28,083 --> 01:33:29,617
AND THERE'S A SIGNIFICANT 

1937
01:33:29,617 --> 01:33:31,586
CHALLENGE HERE THAT HAS NOT YET 

1938
01:33:31,586 --> 01:33:32,187
BEEN FULLY APPRECIATED OR 

1939
01:33:32,187 --> 01:33:36,358
SOLVED.

1940
01:33:36,358 --> 01:33:40,762
SO FINALLY TO WIPE THIS OUT, I 

1941
01:33:40,762 --> 01:33:47,235
THINK I WANT TO TAKE A MINUTE TO

1942
01:33:47,235 --> 01:33:54,342
REFLECT ON HOW REMARKABLE THIS 

1943
01:33:54,342 --> 01:33:56,011
EXPERIENCE HAS BEEN AND ALONG 

1944
01:33:56,011 --> 01:33:57,846
THE WAY WE'VE BEEN JOINED BY 

1945
01:33:57,846 --> 01:34:01,549
OTHER REMARKABLE FOLKS AND THIS 

1946
01:34:01,549 --> 01:34:03,618
IS A SCREEN SHOT OF OUR MONDAY 

1947
01:34:03,618 --> 01:34:05,253
LAB MEETINGS.

1948
01:34:05,253 --> 01:34:07,322
THIS IS FROM YESTERDAY THAT WE 

1949
01:34:07,322 --> 01:34:09,124
HAVE PRETTY MUCH EVERY MONDAY AT

1950
01:34:09,124 --> 01:34:14,596
4:00 INVOLVING SAMMY, OUR 

1951
01:34:14,596 --> 01:34:25,073
WONDERFUL HEROIC FIGURE AND 

1952
01:34:32,080 --> 01:34:34,049
DAVID LU AND WE HAVE THE BEST 

1953
01:34:34,049 --> 01:34:35,283
CHEERLEADER FOR OPTIMISM I'VE 

1954
01:34:35,283 --> 01:34:37,886
SEEN IN A LONG TIME AND THIS IS 

1955
01:34:37,886 --> 01:34:45,026
FIVE OF US BECAUSE IF REALLY 

1956
01:34:45,026 --> 01:34:46,995
LOOKED AT ALL THE COLLABORATORS 

1957
01:34:46,995 --> 01:34:49,431
ON THIS AND I COULD SPEAK TO ALL

1958
01:34:49,431 --> 01:34:52,000
THOSE IN MY LAB IN THE LAST 25 

1959
01:34:52,000 --> 01:34:53,802
YEARS AND BOSTON CHILDREN'S 

1960
01:34:53,802 --> 01:34:55,837
HOSPITAL AND ALL THOSE THAT MADE

1961
01:34:55,837 --> 01:34:58,673
THIS POSSIBLE AND THE NATURAL 

1962
01:34:58,673 --> 01:35:00,408
HISTORY STUDY AND DAVID'S LAB 

1963
01:35:00,408 --> 01:35:01,910
WITH HIS CONTRIBUTIONS AND 

1964
01:35:01,910 --> 01:35:03,378
PEOPLE PART OF THE PROGERIA 

1965
01:35:03,378 --> 01:35:08,550
RESEARCH COMMUNITY, THIS IS 

1966
01:35:08,550 --> 01:35:19,094
REALLY A REMARKABLE EXPERIENCE.

1967
01:35:22,597 --> 01:35:26,534
>> IT'S WHAT YOU SAID,
EVERY 

1968
01:35:26,534 --> 01:35:26,768
MONDAY.

1969
01:35:26,768 --> 01:35:29,871
HOW MANY YEARS HAVE WE BEEN AT 

1970
01:35:29,871 --> 01:35:30,238
THIS?

1971
01:35:30,238 --> 01:35:32,340
SIX YEARS.

1972
01:35:32,340 --> 01:35:33,475
WE'RE STILL MEETING EVERY MONDAY

1973
01:35:33,475 --> 01:35:35,710
AND IT'S A SLOG.

1974
01:35:35,710 --> 01:35:36,277
IT'S DIFFICULT.

1975
01:35:36,277 --> 01:35:41,249
NOTHING -- EVERYBODY IN THE 

1976
01:35:41,249 --> 01:35:44,018
ROOM, NOTHING ABOUT SCIENCE IS 

1977
01:35:44,018 --> 01:35:45,887
IT'S DIFFICULT BUT COMPLETELY 

1978
01:35:45,887 --> 01:35:51,993
WORTH IT.

1979
01:35:51,993 --> 01:35:53,895
SAMMY, HE'S ONE YEAR WITH THIS 

1980
01:35:53,895 --> 01:35:56,231
GROUP A COUPLE YEARS AGO.

1981
01:35:56,231 --> 01:35:59,134
>> IT'S 11:30 AT SAMMY'S
HOUSE 

1982
01:35:59,134 --> 01:36:00,135
RIGHT NOW.

1983
01:36:00,135 --> 01:36:02,370
>> SAMMY, DO YOU WANT TO
SAY 

1984
01:36:02,370 --> 01:36:04,739
ANYTHING ABOUT THHIS?

1985
01:36:04,739 --> 01:36:08,076
CAN YOU SEE THIS PHOTO FROM 

1986
01:36:08,076 --> 01:36:08,810
YESTERDAY?

1987
01:36:08,810 --> 01:36:10,945
>> I DON'T WANT TO BE RUDE
BUT 

1988
01:36:10,945 --> 01:36:17,719
I'M PROUD TO BE PART OF THIS 

1989
01:36:17,719 --> 01:36:17,919
GROUP.

1990
01:36:17,919 --> 01:36:21,656
MY FIRST -- 

1991
01:36:21,656 --> 01:36:22,323
>> THERE'S A 30-SECOND
DELAY NO 

1992
01:36:22,323 --> 01:36:25,593
PROBLEM.

1993
01:36:25,593 --> 01:36:32,233
>> OKAY.

1994
01:36:32,233 --> 01:36:34,736
IT'S BEAUTIFUL TO BE PART OF 

1995
01:36:34,736 --> 01:36:38,506
THIS GROUP BECAUSE FIRST IT WAS 

1996
01:36:38,506 --> 01:36:40,508
ABOUT CRISPR CAS 9 AND NOW I'M 

1997
01:36:40,508 --> 01:36:41,409
COLLABORATING WITH THEM AND YOU 

1998
01:36:41,409 --> 01:36:43,611
WITH PERFORMING THE NEW 

1999
01:36:43,611 --> 01:36:48,183
TECHNIQUE FINALLY, LESLIE, I CAN

2000
01:36:48,183 --> 01:36:50,685
UNDERSTAND WHAT YOU'RE TALKING 

2001
01:36:50,685 --> 01:36:51,719
ABOUT SCIENTIFICALLY AND 

2002
01:36:51,719 --> 01:36:54,989
FRANCIS, WHEN YOU ASK ME WHAT DO

2003
01:36:54,989 --> 01:36:58,159
YOU THINK BIT I'M ALWAYS MIND 

2004
01:36:58,159 --> 01:37:00,495
BLOWN BECAUSE I THINK IF FRANCIS

2005
01:37:00,495 --> 01:37:02,897
WANTS MY OPINION I'M DOING A 

2006
01:37:02,897 --> 01:37:03,765
GOOD JOB.

2007
01:37:03,765 --> 01:37:07,235
IT'S INCREDIBLE TO SEE THE 

2008
01:37:07,235 --> 01:37:08,603
EFFORT OF EVERYONE.

2009
01:37:08,603 --> 01:37:11,139
THIS IS WHAT IT MEANS FOR ME TO 

2010
01:37:11,139 --> 01:37:12,307
BE A COMMUNITY AND IT IS NOT 

2011
01:37:12,307 --> 01:37:16,444
JUST ABOUT MY DISEASE RIGHT NOW 

2012
01:37:16,444 --> 01:37:18,313
BECAUSE I KNOW GENETIC THERAPY 

2013
01:37:18,313 --> 01:37:20,848
WILL NOT BE FOR ME BECAUSE I'M 

2014
01:37:20,848 --> 01:37:21,015
28.

2015
01:37:21,015 --> 01:37:23,918
I CAN HELP WITH THIS BUT IT IS 

2016
01:37:23,918 --> 01:37:26,988
NOT FOR ME BUT FOR THE NEW 

2017
01:37:26,988 --> 01:37:29,857
GENERATIONS, NOW I CAN SAY AS A 

2018
01:37:29,857 --> 01:37:32,627
SCIENTIST THERE'S PROGERIA GAVE 

2019
01:37:32,627 --> 01:37:38,466
ME A REASON OF LIFE AND I'M 

2020
01:37:38,466 --> 01:37:42,170
SEEING SO MANY PEOPLE SAD 

2021
01:37:42,170 --> 01:37:44,372
BECAUSE THEY'RE NOT REASON AND 

2022
01:37:44,372 --> 01:37:45,640
I'M LUCKY TO HAVE A REASON OF 

2023
01:37:45,640 --> 01:37:45,840
LIFE.

2024
01:37:45,840 --> 01:37:53,948
>> THANK YOU, SAMMY.

2025
01:37:53,948 --> 01:37:57,485
>> I THINK YOU ALSO ECHOED
SOME 

2026
01:37:57,485 --> 01:37:59,287
OF THE MOST REMARKABLE 

2027
01:37:59,287 --> 01:38:02,924
STATEMENTS FROM YOUR FRIEND SAM 

2028
01:38:02,924 --> 01:38:05,360
AND IF PEOPLE HAVE NOT HAD THE 

2029
01:38:05,360 --> 01:38:07,228
CHANCE TO LEARN LIFE ACCORDING 

2030
01:38:07,228 --> 01:38:08,963
TO SAM IT'S SOMETHING EVERYBODY 

2031
01:38:08,963 --> 01:38:16,871
SHOULD TAKE TIME TO WATCH YOUR 

2032
01:38:16,871 --> 01:38:17,939
FAMILY.

2033
01:38:17,939 --> 01:38:20,441
SAM, HIS PHILOSOPHY FOR A HAPPY 

2034
01:38:20,441 --> 01:38:23,177
LIFE WAS IN A TED X THAT HAD 

2035
01:38:23,177 --> 01:38:25,813
MORE THAN 100 MILLION DOWNLOADS.

2036
01:38:25,813 --> 01:38:28,449
>> 100 MILLION VIEWS AND
EDGED 

2037
01:38:28,449 --> 01:38:31,519
OUT BILL GATES, JUST WANT TO 

2038
01:38:31,519 --> 01:38:31,886
SAY.

2039
01:38:31,886 --> 01:38:34,322
>> HE HAD A SET OF 

2040
01:38:34,322 --> 01:38:36,124
RECOMMENDATIONS, FOUR OF THEM.

2041
01:38:36,124 --> 01:38:38,626
BE OKAY WITH WHAT YOU ULTIMATELY

2042
01:38:38,626 --> 01:38:39,527
CAN'T DO BECAUSE THERE'S SO MUCH

2043
01:38:39,527 --> 01:38:40,728
YOU CAN DO.

2044
01:38:40,728 --> 01:38:43,298
SURROUND YOURSELF WITH PEOPLE 

2045
01:38:43,298 --> 01:38:47,368
YOU WANT TO BE AROUND, KEEP 

2046
01:38:47,368 --> 01:38:48,303
MOVING FORWARD AND YOU THINK 

2047
01:38:48,303 --> 01:38:51,272
THAT SEEMS TO COVER IT ALL.

2048
01:38:51,272 --> 01:38:52,040
WHAT'S NUMBER FOUR?

2049
01:38:52,040 --> 01:38:54,409
NEVER MISS A PARTY IF YOU CAN 

2050
01:38:54,409 --> 01:38:56,244
HELP IT AND THAT'S THE WAY SAM 

2051
01:38:56,244 --> 01:38:58,413
LIVED HIS LIFE AND I KNOW HE 

2052
01:38:58,413 --> 01:39:00,181
WOULD WANT ALL OF US TO DO THE 

2053
01:39:00,181 --> 01:39:00,648
SAME.

2054
01:39:00,648 --> 01:39:02,750
THAT'S KIND OF WHERE WE WANTED 

2055
01:39:02,750 --> 01:39:03,885
TO BRING THIS TO THE POINT MAYBE

2056
01:39:03,885 --> 01:39:07,622
OF QUESTIONS IF THERE ARE SOME.

2057
01:39:07,622 --> 01:39:09,490
THERE ARE SOME WE COULD HEAR 

2058
01:39:09,490 --> 01:39:10,625
ABOUT BEFORE WE LET EVERYBODY 

2059
01:39:10,625 --> 01:39:11,926
FADEAWAY FROM HERE.

2060
01:39:11,926 --> 01:39:13,995
>> I WANTED TO REMEMBER
PEOPLE 

2061
01:39:13,995 --> 01:39:16,564
ONLINE A LOT OF PEOPLE OUTSIDE 

2062
01:39:16,564 --> 01:39:19,834
THE NIH WATCHING THERE'S A SEND 

2063
01:39:19,834 --> 01:39:22,370
LIVE FEEDBACK BUTTON NOT 

2064
01:39:22,370 --> 01:39:25,373
INTUITIVE TO ASK QUESTIONS BUT 

2065
01:39:25,373 --> 01:39:26,808
THAT'S HOW YOU ASK QUESTIONS AND

2066
01:39:26,808 --> 01:39:29,777
THEY COME TO US IN THE ROOM.

2067
01:39:29,777 --> 01:39:32,347
>> WE DO HAVE SOME
PROVOCATIVE 

2068
01:39:32,347 --> 01:39:33,214
AND INTERESTING -- 

2069
01:39:33,214 --> 01:39:35,049
>> THERE'S PEOPLE IN THE
ROOM 

2070
01:39:35,049 --> 01:39:35,583
ALSO.

2071
01:39:35,583 --> 01:39:36,818
>> ANYONE IN THE ROOM?

2072
01:39:36,818 --> 01:39:42,824
>> PLEASE GO TO THE
MICROPHONE 

2073
01:39:42,824 --> 01:39:53,134
IF YOU HAVE -- SO 

2074
01:40:02,944 --> 01:40:05,580
>> SAM'S VERY BRIGHT, VERY

2075
01:40:05,580 --> 01:40:05,913
INTELLIGENT.

2076
01:40:05,913 --> 01:40:10,918
A LOT OF THE STUFF YOU'RE 

2077
01:40:10,918 --> 01:40:13,788
TALKING ABOUT WITH THE CLASSIC 

2078
01:40:13,788 --> 01:40:15,523
STROKES AND CARDIOVASCULAR IERZ,

2079
01:40:15,523 --> 01:40:19,227
I NOTICED YOU GUYS WEREN'T 

2080
01:40:19,227 --> 01:40:21,796
TALKING ABOUT NEUROLOGICAL 

2081
01:40:21,796 --> 01:40:25,867
PATHOLOGIES.

2082
01:40:25,867 --> 01:40:28,803
WHY IS THAT?

2083
01:40:28,803 --> 01:40:30,905
FRANCIS: YOU'RE RIGHT, DIM EN IS

2084
01:40:30,905 --> 01:40:31,839
THAT DOESN'T SEEM TO BE PART OF 

2085
01:40:31,839 --> 01:40:33,574
THE CONDITION BUT STROKES CAN BE

2086
01:40:33,574 --> 01:40:35,710
PART OF THE NEUROLOGICAL 

2087
01:40:35,710 --> 01:40:37,578
PROBLEM.

2088
01:40:37,578 --> 01:40:39,080
LES

2089
01:40:39,080 --> 01:40:41,883
LESLIE: PROGERIN IS EXPRESSED IN

2090
01:40:41,883 --> 01:40:45,586
THE VASCULATURE OF THE BRAIN BUT

2091
01:40:45,586 --> 01:40:47,422
NOT THE BRAIN.

2092
01:40:47,422 --> 01:40:51,392
SOME BEAUTIFUL WORK PUBLISHED 

2093
01:40:51,392 --> 01:40:52,794
YEARS AGO DISCOVERED MICRORNA 

2094
01:40:52,794 --> 01:40:56,230
THAT EXPRESSES PROGERIN IN THE 

2095
01:40:56,230 --> 01:40:56,731
BRAIN.

2096
01:40:56,731 --> 01:40:59,267
THE BRAIN AND THE NEUROLOGICAL 

2097
01:40:59,267 --> 01:41:00,134
SYSTEM ARE NORMAL.

2098
01:41:00,134 --> 01:41:02,570
LIVER FUNCTION, KIDNEY FUNCTION,

2099
01:41:02,570 --> 01:41:04,839
IMMUNE FUNCTION AND 

2100
01:41:04,839 --> 01:41:06,474
GASTROINTESTINAL FUNCTION ARE 

2101
01:41:06,474 --> 01:41:07,542
NORMAL WHICH HELPS US A LOT 

2102
01:41:07,542 --> 01:41:08,509
CLINICAL TRIALS.

2103
01:41:08,509 --> 01:41:10,778
AS A CONSEQUENCE OF COURSE, 

2104
01:41:10,778 --> 01:41:11,345
THEY'RE ALL BRILLIANT, JUST 

2105
01:41:11,345 --> 01:41:17,885
SAYING.

2106
01:41:17,885 --> 01:41:21,689
>> IF YOU PULL DOWN THE
SLIDE --

2107
01:41:21,689 --> 01:41:23,224
HOW WOULD YOU SUGGEST WE PULL 

2108
01:41:23,224 --> 01:41:26,861
DOWN BECAUSE I'M AFRAID WE'LL 

2109
01:41:26,861 --> 01:41:37,238
HIT THE WRONG BUTTON.

2110
01:41:46,814 --> 01:41:48,316
>> LAMIN A SOUNDS LIKE THE

2111
01:41:48,316 --> 01:41:49,484
MAINLY PLAYER.

2112
01:41:49,484 --> 01:41:51,285
HAVE YOU LOOKED AT ANY OTHER 

2113
01:41:51,285 --> 01:41:54,489
POSSIBLY CONTRIBUTING TARGETS OR

2114
01:41:54,489 --> 01:41:58,726
HAS LAMIN A JUST BEEN IT?

2115
01:41:58,726 --> 01:42:01,496
>> THERE'S PROGEROID
SYNDROME 

2116
01:42:01,496 --> 01:42:02,864
AFFECT OTHER PARTS OF THIS 

2117
01:42:02,864 --> 01:42:03,397
PATHWAY.

2118
01:42:03,397 --> 01:42:05,700
THE ENZYME I MENTIONED THAT DOES

2119
01:42:05,700 --> 01:42:09,337
THE CLEAVAGE, IF THAT'S NOT 

2120
01:42:09,337 --> 01:42:11,105
PRESENT IT GIVES A RATHER SEVERE

2121
01:42:11,105 --> 01:42:13,975
SOMETHING CALLED RESTRICTIVE 

2122
01:42:13,975 --> 01:42:17,979
DERMOPATHY WITH HAS OVERLAP 

2123
01:42:17,979 --> 01:42:20,815
BECAUSE YOU DON'T DO THE 

2124
01:42:20,815 --> 01:42:21,849
CLEAVAGE AND HAVE LAMIN A 

2125
01:42:21,849 --> 01:42:26,721
BECAUSE THE ENZYME WASN'T THERE 

2126
01:42:26,721 --> 01:42:29,156
TO HELP IT I JUST READ A PAPER 

2127
01:42:29,156 --> 01:42:30,057
LAST NIGHT THERE'S A PATIENT 

2128
01:42:30,057 --> 01:42:35,463
DESCRIBED AS A POINT MUTATION IN

2129
01:42:35,463 --> 01:42:41,602
THAT AND THERE'S A LAMINOPATHY 

2130
01:42:41,602 --> 01:42:43,204
THAT LOOKS LIKE A MILDER VERSION

2131
01:42:43,204 --> 01:42:51,812
AND IT WORKS A LITTLE BIT.

2132
01:42:51,812 --> 01:42:57,351
AND THERE'S SIMILAR TYPES AND A 

2133
01:42:57,351 --> 01:42:59,887
CURATOR OF MOST OF THOSE.

2134
01:42:59,887 --> 01:43:01,756
>> IN ADDITION YOU'RE
TALKING 

2135
01:43:01,756 --> 01:43:03,090
ABOUT DOWN STREAM TARGETS 

2136
01:43:03,090 --> 01:43:10,932
BECAUSE YOU HAVE SO MANY DOWN 

2137
01:43:10,932 --> 01:43:20,341
STREAM AND WHICH ARE IN REASON 

2138
01:43:20,341 --> 01:43:21,943
TO THE PATHOLOGY AND WHAT WILL 

2139
01:43:21,943 --> 01:43:25,046
YOU HIT IF YOUR DRUG IS DOWN 

2140
01:43:25,046 --> 01:43:25,246
HERE?

2141
01:43:25,246 --> 01:43:30,184
A LOT OF DISEASES HAVE 

2142
01:43:30,184 --> 01:43:33,287
TREATMENTS THAT ARE EFFECTIVE 

2143
01:43:33,287 --> 01:43:34,722
DOWN STREAM BECAUSE THEY CAN'T 

2144
01:43:34,722 --> 01:43:35,489
CORRECT THE GENE.

2145
01:43:35,489 --> 01:43:40,761
WE'RE TALKING ABOUT THE RNA AND 

2146
01:43:40,761 --> 01:43:43,164
DNA THERAPIES AND THERE'S A LOT 

2147
01:43:43,164 --> 01:43:48,302
OF EXPRESSION PROFILES HAVE BEEN

2148
01:43:48,302 --> 01:43:50,304
DONE I'M SURE THEY'RE THERE BUT 

2149
01:43:50,304 --> 01:43:58,646
IT'S TOUGH STUFF.

2150
01:43:58,646 --> 01:44:00,715
WHAT ARE THE IMPLICATIONS FOR 

2151
01:44:00,715 --> 01:44:01,682
AGING IN THE GENERAL POPULATION 

2152
01:44:01,682 --> 01:44:06,687
BASED ON THE RESEARCH FINDINGS 

2153
01:44:06,687 --> 01:44:09,790
AND CLINICAL TRIALS.

2154
01:44:09,790 --> 01:44:20,301
>> WE'RE PLANNING TO PUT
THE 

2155
01:44:23,437 --> 01:44:25,773
MEDICATION IN THE WATER.

2156
01:44:25,773 --> 01:44:27,341
PEOPLE WONDERED WILL PROGERIA 

2157
01:44:27,341 --> 01:44:30,044
TEACH US SOMETHING ABOUT NORMAL 

2158
01:44:30,044 --> 01:44:34,115
AGING OR IS IT A DRAMATIC 

2159
01:44:34,115 --> 01:44:34,782
PHENOCOPY.

2160
01:44:34,782 --> 01:44:37,018
IT HAS A CONNECTION AND THE 

2161
01:44:37,018 --> 01:44:39,920
NATURE OF THE CRYPTIC SPLICE 

2162
01:44:39,920 --> 01:44:40,821
DONOR.

2163
01:44:40,821 --> 01:44:42,523
WOULD IT BENEFIT US TO BE ABLE 

2164
01:44:42,523 --> 01:44:53,000
TO KNOCK THAT BACK AND SEE?

2165
01:44:54,535 --> 01:44:57,338
YOU CAN MUTATE THE NUCLEOTIDES 

2166
01:44:57,338 --> 01:44:59,473
SO WE'RE CURIOUS TO SEE DOES THE

2167
01:44:59,473 --> 01:45:01,676
MOUSE LIVE FOREVER OR LIVE 

2168
01:45:01,676 --> 01:45:03,811
LONGER THAN A WILD TYPE MOUSE OR

2169
01:45:03,811 --> 01:45:05,179
ALTERNATIVELY, THINK ABOUT THIS,

2170
01:45:05,179 --> 01:45:07,615
IT DOES SEEM LIKE THIS IS PART 

2171
01:45:07,615 --> 01:45:08,816
OF PROGRAM SENESCENCE.

2172
01:45:08,816 --> 01:45:10,785
THIS IS NOT AN ACCIDENT.

2173
01:45:10,785 --> 01:45:12,386
CELLS HAVE A MECHANISM WHEN 

2174
01:45:12,386 --> 01:45:13,754
THEY'RE JUST ABOUT DONE TO BE 

2175
01:45:13,754 --> 01:45:16,657
REALLY DONE AND TO HEAD TO THE 

2176
01:45:16,657 --> 01:45:21,729
EXIT AND YOU CAN SOMETHING WHAT 

2177
01:45:21,729 --> 01:45:29,770
THAT MIGHT BE.

2178
01:45:29,770 --> 01:45:31,338
WILL THE ANIMALS HAVE A HIGHER 

2179
01:45:31,338 --> 01:45:31,739
RISK OF CANCER?

2180
01:45:31,739 --> 01:45:32,707
I DON'T KNOW.

2181
01:45:32,707 --> 01:45:34,241
WE NEED TO UNDERSTAND THAT 

2182
01:45:34,241 --> 01:45:34,508
BETTER.

2183
01:45:34,508 --> 01:45:36,744
CERTAINLY IT IS FAIR TO SAY WHAT

2184
01:45:36,744 --> 01:45:39,380
WE'VE LEARNED ABOUT PROGERIN HAS

2185
01:45:39,380 --> 01:45:40,948
SHED A LOT OF IMPORTANT LIGHT ON

2186
01:45:40,948 --> 01:45:43,217
THE NORMAL AGING PROCESS NOT YET

2187
01:45:43,217 --> 01:45:44,251
TO THE POINT OF SAYING HERE'S 

2188
01:45:44,251 --> 01:45:46,654
WHAT WE SHOULD DO ABOUT IT BUT 

2189
01:45:46,654 --> 01:45:48,989
HOW TO UNDERSTAND IT SO THE 

2190
01:45:48,989 --> 01:45:51,826
AGING INSTITUTE WHICH HAS BEEN A

2191
01:45:51,826 --> 01:45:53,260
BIG SUPPORTER OF EXTRAMURAL 

2192
01:45:53,260 --> 01:45:57,998
SUPPORT IN PROGERIA HAS BEEN A 

2193
01:45:57,998 --> 01:45:59,266
GREAT PARTNER.

2194
01:45:59,266 --> 01:46:01,202
>> THEY'VE SUPPORTED A LOT
OF 

2195
01:46:01,202 --> 01:46:03,370
OUR SCIENTIFIC MEETINGS.

2196
01:46:03,370 --> 01:46:06,907
THERE'S ELEGANT STUDIES DONE TO 

2197
01:46:06,907 --> 01:46:17,418
START TO GET AT THE QUESTION.

2198
01:46:19,320 --> 01:46:20,654
PROGERIN IS EXPRESSED IN ALL 

2199
01:46:20,654 --> 01:46:25,392
LAYERS AND INCREASES AT 3% PER 

2200
01:46:25,392 --> 01:46:28,696
YEAR IN THE VASCULATURE AND 

2201
01:46:28,696 --> 01:46:29,830
FREQUENCY.

2202
01:46:29,830 --> 01:46:33,467
THERE WAS A STUDY ON HUMAN 

2203
01:46:33,467 --> 01:46:35,136
BIOPSIES AND LOOKED FOR PROGERIN

2204
01:46:35,136 --> 01:46:37,605
AND IF YOU LOOKED AT A  

2205
01:46:37,605 --> 01:46:42,510
6-YEAR-OLD AND  7-YEAR-OLD AND 

2206
01:46:42,510 --> 01:46:44,311
BY THE TIME TO 80 OR 90 YEARS 

2207
01:46:44,311 --> 01:46:47,114
OLD THERE WERE CELLS ALL OVER 

2208
01:46:47,114 --> 01:46:48,849
THE SKIN WITH PROGERIN 

2209
01:46:48,849 --> 01:46:49,416
EXPRESSION.

2210
01:46:49,416 --> 01:46:54,555
IT BUILDS UP WITH AGE.

2211
01:46:54,555 --> 01:46:57,124
IT'S THERE.

2212
01:46:57,124 --> 01:46:58,125
WHAT IT MEANS AND IF YOU 

2213
01:46:58,125 --> 01:47:00,161
MANIPULATE IT TO THE BENEFIT OF 

2214
01:47:00,161 --> 01:47:10,638
SHOULD BE AN AREA OF STUDY.

2215
01:47:11,806 --> 01:47:15,910
>> WHAT SYMPTOMS USUALLY
BRING A

2216
01:47:15,910 --> 01:47:20,681
PROGERIA PATIENT TO CONSULT AND 

2217
01:47:20,681 --> 01:47:22,483
DO WE KNOW WHAT PLASMA PROGERIN 

2218
01:47:22,483 --> 01:47:25,686
IS FROM THE STANDPOINT OF IT 

2219
01:47:25,686 --> 01:47:35,396
BEING DIAGNOSTIC?

2220
01:47:35,396 --> 01:47:38,566
>> WHEN SAM WAS FIRST
DIAGNOSED 

2221
01:47:38,566 --> 01:47:42,369
IT TAKES -- PARENT OF KIDS WITH 

2222
01:47:42,369 --> 01:47:43,604
RARE DISEASES KNOW THIS YOU GO 

2223
01:47:43,604 --> 01:47:46,173
FROM DOCTOR TO DOCTOR AND TEST 

2224
01:47:46,173 --> 01:47:47,741
AFTER TEST.

2225
01:47:47,741 --> 01:47:51,312
BUT NOW PROGERIA IS IN 

2226
01:47:51,312 --> 01:47:53,781
HARRISON'S, IT'S IN TEXTBOOK AND

2227
01:47:53,781 --> 01:47:55,716
TAUGHT IN MIDDLE SCHOOL AND 

2228
01:47:55,716 --> 01:47:56,951
MEDICAL SCHOOL.

2229
01:47:56,951 --> 01:47:59,954
IT WASN'T TAUGHT BACK THEN AND 

2230
01:47:59,954 --> 01:48:04,692
KIDS ARE DIAGNOSED EARLIER AND 

2231
01:48:04,692 --> 01:48:06,927
THE SKIN SIGNS -- THERE ARE SKIN

2232
01:48:06,927 --> 01:48:08,796
SIGNS DERMATOLOGISTS ARE VERY 

2233
01:48:08,796 --> 01:48:10,531
VISUAL PEOPLE SO SKIN SIGNS ARE 

2234
01:48:10,531 --> 01:48:12,199
OFTEN SOME OF THE FIRST SIGNS.

2235
01:48:12,199 --> 01:48:13,434
GROWTH FALLS OFF TOO AND THAT 

2236
01:48:13,434 --> 01:48:15,202
COULD BE THE FIRST SIGNS BUT THE

2237
01:48:15,202 --> 01:48:19,573
EARLIER KIDS, IT'S THE SKIN 

2238
01:48:19,573 --> 01:48:19,907
SIGNS.

2239
01:48:19,907 --> 01:48:25,779
WHAT WAS THE SECOND QUESTION?

2240
01:48:25,779 --> 01:48:36,123
>> WE WANT VALIDATED FOR
THE 

2241
01:48:36,123 --> 01:48:37,524
CLINICAL TRIALS BECAUSE WE HAVE 

2242
01:48:37,524 --> 01:48:47,801
A GENETIC TEST.

2243
01:48:49,870 --> 01:48:51,405
ABOUT 10% COME FROM MUTATION AND

2244
01:48:51,405 --> 01:48:52,506
IF YOU WANT TO KNOW WHAT'S GOING

2245
01:48:52,506 --> 01:49:02,883
ON, SEQUENCE THE GENE.

2246
01:49:04,018 --> 01:49:04,084
 

2247
01:49:04,084 --> 01:49:08,822
>> I CAME TO THE LECTURE
NOT 

2248
01:49:08,822 --> 01:49:11,025
BECAUSE I KNOW SOMEBODY WITH 

2249
01:49:11,025 --> 01:49:17,564
PROGERIA OR BECAUSE FRANCIS IS 

2250
01:49:17,564 --> 01:49:24,538
SPEAKING BUT THERE'S INTERESTING

2251
01:49:24,538 --> 01:49:29,610
IN THIS AND I WORK ON A FORM OF 

2252
01:49:29,610 --> 01:49:32,980
HEPATITIS AND THERE'S AN ANTIGEN

2253
01:49:32,980 --> 01:49:35,883
AND THERE'S EFFORTS TRYING TO 

2254
01:49:35,883 --> 01:49:37,985
TREAT DELTA VIRUS INFECTION AND 

2255
01:49:37,985 --> 01:49:39,286
THERE COULD BE OTHER EXAMPLES OF

2256
01:49:39,286 --> 01:49:44,558
OTHER VIRAL INFECTIONS.

2257
01:49:44,558 --> 01:49:45,192
I'M INTERESTED IN YOUR 

2258
01:49:45,192 --> 01:49:47,561
PERSPECTIVE IF THAT'S THE CASE 

2259
01:49:47,561 --> 01:49:53,901
IS THAT A WORTHWHILE APPROACH TO

2260
01:49:53,901 --> 01:49:59,039
DEVELOP ANTIVIRALS TARGETING THE

2261
01:49:59,039 --> 01:50:02,776
CELLULAR PROCESS INSTEAD OF 

2262
01:50:02,776 --> 01:50:03,377
ANTIVIRAL THERAPY.

2263
01:50:03,377 --> 01:50:07,281
>> IT'S A CRITICAL STEP IN
THE 

2264
01:50:07,281 --> 01:50:09,116
ABILITY TO INVADE THE NEXT CELL.

2265
01:50:09,116 --> 01:50:10,150
HAVE YOU THE SIDE EFFECTS THAT 

2266
01:50:10,150 --> 01:50:12,519
WILL HAPPEN AND SAMMY COULD TELL

2267
01:50:12,519 --> 01:50:17,658
YOU WHEN HE FIRST GOT STARTED ON

2268
01:50:17,658 --> 01:50:19,159
LONAFARNIB IT WASN'T THAT 

2269
01:50:19,159 --> 01:50:20,627
PLEASANT UNTIL YOUR BODY GETS 

2270
01:50:20,627 --> 01:50:23,230
USED TO THEM.

2271
01:50:23,230 --> 01:50:24,665
THE REASON IT DIDN'T WORK FOR 

2272
01:50:24,665 --> 01:50:26,867
CANCER OR RAS AND THIS GETS IN 

2273
01:50:26,867 --> 01:50:28,936
THE NITTY-GRITTY, THERE'S 

2274
01:50:28,936 --> 01:50:36,310
ANOTHER WAY OF ATTACHING A THIGH

2275
01:50:36,310 --> 01:50:38,112
HYDROPHOBIC TRAIL AND WITH RAS 

2276
01:50:38,112 --> 01:50:43,851
YOU COULD DO BOTH AND LOOK AT 

2277
01:50:43,851 --> 01:50:53,894
THE THIS AND -- 

2278
01:50:53,894 --> 01:50:55,829
>> THAT WAS THE PRIMARY 

2279
01:50:55,829 --> 01:50:59,767
INTEREST.

2280
01:50:59,767 --> 01:51:02,803
THAT WAS THE HEPATITIS DELTA.

2281
01:51:02,803 --> 01:51:12,780
THAT DIDN'T GO AS PLANNED.

2282
01:51:12,780 --> 01:51:14,715
>> THERE'S OTHER PROCESS.

2283
01:51:14,715 --> 01:51:19,520
>> IF IT WORKED FOR
PROGERIA IT 

2284
01:51:19,520 --> 01:51:23,924
MAY WORK FOR SOMETHING ELSE.

2285
01:51:23,924 --> 01:51:28,228
>> LONAFARNIB DIDN'T GET
MUCH 

2286
01:51:28,228 --> 01:51:29,063
EXPERIENCE FOR OTHER THINGS AND 

2287
01:51:29,063 --> 01:51:36,403
NOW IT'S FDA APPROVED.

2288
01:51:36,403 --> 01:51:37,604
>> THERE'S QUESTIONS
WHETHER 

2289
01:51:37,604 --> 01:51:40,674
PROGERIA IS AN INHERITED 

2290
01:51:40,674 --> 01:51:42,743
DISEASE.

2291
01:51:42,743 --> 01:51:45,946
>> WE CALL IT OUT
AUTOSOMAL 

2292
01:51:45,946 --> 01:51:47,981
DOMINANT BUT HAS NEVER BEEN 

2293
01:51:47,981 --> 01:51:50,884
INHERITED FROM A PARENT TO A 

2294
01:51:50,884 --> 01:51:53,387
CHILD BECAUSE PEOPLE WITH IT 

2295
01:51:53,387 --> 01:51:55,456
HAVE NOT PRODUCED AND IT'S DE 

2296
01:51:55,456 --> 01:51:58,058
NOVO FROM THE WAY WE UNDERSTAND 

2297
01:51:58,058 --> 01:52:00,060
THE EFFECT OF THE DOMINANT 

2298
01:52:00,060 --> 01:52:02,663
NEGATIVE PROTEIN IF YOU WERE 

2299
01:52:02,663 --> 01:52:05,766
ABLE TO REPRODUCE WITH THIS IT'D

2300
01:52:05,766 --> 01:52:08,769
BE A 50/50 CHANCE AND IT'S 

2301
01:52:08,769 --> 01:52:10,604
CORRECT TO CALL IT AUTOSOMAL 

2302
01:52:10,604 --> 01:52:12,639
DOMINANT BUT CONFUSES PEOPLE 

2303
01:52:12,639 --> 01:52:14,041
ABOUT THE VERTICAL 

2304
01:52:14,041 --> 01:52:14,408
TRANSMISSIONS.

2305
01:52:14,408 --> 01:52:16,844
WE'VE NEVER SEEN ONE BUT AT SOME

2306
01:52:16,844 --> 01:52:17,911
POINT MAYBE WE WILL.

2307
01:52:17,911 --> 01:52:19,179
>> WE ONLY HAVE A FEW
MINUTES 

2308
01:52:19,179 --> 01:52:21,915
LEFT AND I KNOW SAMMY HAD ASKED 

2309
01:52:21,915 --> 01:52:24,518
TO ASK US A FEW QUESTIONS.

2310
01:52:24,518 --> 01:52:27,788
GO FOR IT, SAMMY.

2311
01:52:27,788 --> 01:52:29,289
>> YEAH, I HAVE TOO MANY 

2312
01:52:29,289 --> 01:52:30,724
QUESTION.

2313
01:52:30,724 --> 01:52:36,296
THE FIRST IS HOW DO YOU DEAL 

2314
01:52:36,296 --> 01:52:37,831
WITH THE FRUSTRATION WHEN THE 

2315
01:52:37,831 --> 01:52:46,173
SCIENTIFIC RESULTS ARE NOT AS 

2316
01:52:46,173 --> 01:52:46,573
EXPECTED.

2317
01:52:46,573 --> 01:52:49,776
THAT'S THE FIRST QUESTION BUT I 

2318
01:52:49,776 --> 01:52:52,412
HAVE ANOTHER ONE.

2319
01:52:52,412 --> 01:52:53,013
>> OKAY, DRIVES ME OUT OF
MY 

2320
01:52:53,013 --> 01:52:58,318
MIND.

2321
01:52:58,318 --> 01:52:59,386
THE SCIENTIFIC RESULTS ARE WHAT 

2322
01:52:59,386 --> 01:53:00,888
THEY ARE.

2323
01:53:00,888 --> 01:53:02,556
I KIND OF THRIVE ON THOSE.

2324
01:53:02,556 --> 01:53:04,258
IF YOU DO THINGS REALLY WELL AND

2325
01:53:04,258 --> 01:53:05,692
GET AN ANSWER ONE WAY OR 

2326
01:53:05,692 --> 01:53:08,428
ANOTHER, IT LEADS YOU SOME 

2327
01:53:08,428 --> 01:53:09,663
PLACE.

2328
01:53:09,663 --> 01:53:16,770
THE BUREAUCRACY, THE MONEY, THE 

2329
01:53:16,770 --> 01:53:19,806
PACE WHEN YOU'RE TRYING TO SAVE 

2330
01:53:19,806 --> 01:53:22,309
LIVES YOUR CHILD OR OTHERS, 

2331
01:53:22,309 --> 01:53:25,279
CHILDREN, IT IS REALLY REALLY 

2332
01:53:25,279 --> 01:53:27,581
DIFFICULT AND I DON'T KNOW YOU 

2333
01:53:27,581 --> 01:53:30,350
JUST PUSH FORWARD AND PUSH OTHER

2334
01:53:30,350 --> 01:53:32,519
PEOPLE I'M A PUSHY GAL SO -- I 

2335
01:53:32,519 --> 01:53:33,587
DON'T KNOW.

2336
01:53:33,587 --> 01:53:35,756
I DON'T KNOW HOW ELSE TO SAY IT.

2337
01:53:35,756 --> 01:53:37,224
IT'S JUST THE TRUTH BUT YOU HAVE

2338
01:53:37,224 --> 01:53:38,692
TO KEEP MOVING FORWARD.

2339
01:53:38,692 --> 01:53:39,793
THAT'S IT.

2340
01:53:39,793 --> 01:53:41,595
>> LESLIE, YOU PUSH PEOPLE
BY 

2341
01:53:41,595 --> 01:53:43,597
LURING THEM INTO THIS PROGRAM 

2342
01:53:43,597 --> 01:53:45,332
AND THEN THEY NEVER LEAVE 

2343
01:53:45,332 --> 01:53:47,467
BECAUSE IT'S TOO COMPELLING.

2344
01:53:47,467 --> 01:53:50,137
I THINK YOU SAID IT WELL.

2345
01:53:50,137 --> 01:53:51,772
THE OTHER THING I'D SAYING ABOUT

2346
01:53:51,772 --> 01:53:54,775
THE SCIENTIFIC FAILURE IS 

2347
01:53:54,775 --> 01:53:55,776
THEY'RE INCREDIBLY DISAPPOINTING

2348
01:53:55,776 --> 01:53:57,644
AND DEVASTATING AND SAY TO 

2349
01:53:57,644 --> 01:53:59,012
YOURSELF I HAVE TO LEARN 

2350
01:53:59,012 --> 01:54:00,914
SOMETHING FROM THIS.

2351
01:54:00,914 --> 01:54:02,382
I HAVE TO FIGURE OUT WHAT 

2352
01:54:02,382 --> 01:54:04,918
HAPPENED HERE AND HOW CAN I USE 

2353
01:54:04,918 --> 01:54:06,520
THAT INFORMATION TO DESIGN THE 

2354
01:54:06,520 --> 01:54:07,554
NEXT APPROACH THAT'S GOING TO BE

2355
01:54:07,554 --> 01:54:09,089
MORE SUCCESSFUL SO I'M FURTHER 

2356
01:54:09,089 --> 01:54:12,859
ALONG THAN I WOULD HAVE.

2357
01:54:12,859 --> 01:54:14,261
>> I DON'T LIKE LOOKING
BACK AND

2358
01:54:14,261 --> 01:54:15,095
SAYING I COULD HAVE DONE THAT 

2359
01:54:15,095 --> 01:54:21,835
BETTER BECAUSE I DO THAT A LOT 

2360
01:54:21,835 --> 01:54:24,705
BUT I TRY TO TURN THAT INTO IN 

2361
01:54:24,705 --> 01:54:26,840
NOT LOOKING BACKWARDS BUT GO 

2362
01:54:26,840 --> 01:54:29,843
FORWARD AND TRY TO PUSH THE 

2363
01:54:29,843 --> 01:54:30,477
DIFFICULT PORTION DOWN A LITTLE 

2364
01:54:30,477 --> 01:54:33,113
BIT.

2365
01:54:33,113 --> 01:54:36,717
WHAT'S YOUR SECOND QUESTION?

2366
01:54:36,717 --> 01:54:40,454
>> SECOND QUESTION IS
ABOUT SAM.

2367
01:54:40,454 --> 01:54:43,123
OF COURSE SAM WAS MY FRIEND.

2368
01:54:43,123 --> 01:54:49,830
HE IS MY FRIEND I PREFER TO SAY.

2369
01:54:49,830 --> 01:54:57,838
AND YOU KNOW I SHOULD THANK GOD 

2370
01:54:57,838 --> 01:55:01,541
FOR PROGERIA FOR PUTTING YOU AND

2371
01:55:01,541 --> 01:55:03,210
SAM IN MY LIFE AND SAM WAS ABLE 

2372
01:55:03,210 --> 01:55:10,550
TO IMPACT THE LIFE OF SO MANY 

2373
01:55:10,550 --> 01:55:10,884
PEOPLE.

2374
01:55:10,884 --> 01:55:12,686
IT'S BEAUTIFUL AND LIFE IS 

2375
01:55:12,686 --> 01:55:13,287
GREAT.

2376
01:55:13,287 --> 01:55:14,888
I WANT TO TRUST YOU BOTH, WHAT 

2377
01:55:14,888 --> 01:55:17,991
IS THE PART OF SAM'S MESSAGE 

2378
01:55:17,991 --> 01:55:22,329
THAT IMPACTED YOU MORE AS A 

2379
01:55:22,329 --> 01:55:25,132
MOTHER AND FRIEND BUT ALSO JUST 

2380
01:55:25,132 --> 01:55:31,571
AS PEOPLE.

2381
01:55:31,571 --> 01:55:33,540
I KNOW IT IS A DIFFICULT 

2382
01:55:33,540 --> 01:55:33,807
QUESTION.

2383
01:55:33,807 --> 01:55:36,209
>> IT'S A GOOD QUESTION
BECAUSE 

2384
01:55:36,209 --> 01:55:38,745
THERE'S A LOT OF FACETS OF THE 

2385
01:55:38,745 --> 01:55:41,715
FRIENDSHIP I HAD WITH SAM I 

2386
01:55:41,715 --> 01:55:43,083
COULD REFLECT ON AS HAVING LEFT 

2387
01:55:43,083 --> 01:55:45,185
A REALLY IMPORTANT LIFE ON MY 

2388
01:55:45,185 --> 01:55:46,286
WHOLE VIEW OF HOW MEDICAL 

2389
01:55:46,286 --> 01:55:51,191
RESEARCH SHOULD BE CONDUCTED.

2390
01:55:51,191 --> 01:55:53,694
IT WAS -- IT WAS IMPATIENCE BUT 

2391
01:55:53,694 --> 01:55:55,962
ALWAYS IN THE MOST GENEROUS WAY.

2392
01:55:55,962 --> 01:55:58,332
YOU CAN BE IMPATIENT AND 

2393
01:55:58,332 --> 01:55:58,665
IRRITATING.

2394
01:55:58,665 --> 01:56:00,233
HE WAS IMPATIENT AND INSPIRED 

2395
01:56:00,233 --> 01:56:01,635
YOU TO TRY TO FIGURE OUT HOW TO 

2396
01:56:01,635 --> 01:56:05,172
GO FASTER AND DO THINGS BETTER 

2397
01:56:05,172 --> 01:56:07,107
BUT ALSO HAD THIS WONDERFUL 

2398
01:56:07,107 --> 01:56:08,275
INFECTIOUS WAY OF LOVING LIFE AS

2399
01:56:08,275 --> 01:56:09,476
YOU DO, SAMMY.

2400
01:56:09,476 --> 01:56:11,812
THE TWO OF YOU CARRY THAT 

2401
01:56:11,812 --> 01:56:13,547
THROUGH ALL YOU'VE BEEN THROUGH 

2402
01:56:13,547 --> 01:56:17,818
IN A REMARKABLE WAY THAT MAKES 

2403
01:56:17,818 --> 01:56:20,287
YOU FEEL HOW CAN I COMPLAIN 

2404
01:56:20,287 --> 01:56:21,588
ABOUT ANYTHING BECAUSE HERE'S 

2405
01:56:21,588 --> 01:56:23,623
TWO YOUNG WHEN WHO COULD HAVE 

2406
01:56:23,623 --> 01:56:24,991
DECIDED I'LL HIDE IN THE CORNER 

2407
01:56:24,991 --> 01:56:28,362
AND INSTEAD HAVE BEEN UP THERE 

2408
01:56:28,362 --> 01:56:31,064
WHETHER WITH 100 MILLION 

2409
01:56:31,064 --> 01:56:32,999
DOWNLOADS ON A TED X OR YOU IN 

2410
01:56:32,999 --> 01:56:34,334
FRONT OF I DON'T KNOW HOW MANY 

2411
01:56:34,334 --> 01:56:37,371
PEOPLE IN PADUA INSPIRING THEM 

2412
01:56:37,371 --> 01:56:39,206
TO THINK ABOUT WHAT THEY COULD 

2413
01:56:39,206 --> 01:56:39,639
DO.

2414
01:56:39,639 --> 01:56:43,577
ALL OF THAT, I GUESS THAT ONE 

2415
01:56:43,577 --> 01:56:44,845
QUOTE IN HIS FOUR STATEMENTS 

2416
01:56:44,845 --> 01:56:48,715
ABOUT THE LESSONS FROM SAM, 

2417
01:56:48,715 --> 01:56:49,850
DON'T FOCUS ON WHAT YOU CAN'T 

2418
01:56:49,850 --> 01:56:51,685
DO, FOCUS ON WHAT YOU CAN.

2419
01:56:51,685 --> 01:56:52,886
HE LIVED THAT IN EVERY WAY.

2420
01:56:52,886 --> 01:56:55,555
HE WAS THE KID WHO WAS IN THE 

2421
01:56:55,555 --> 01:56:57,391
MARCHING BAND FOR HIGH SCHOOL 

2422
01:56:57,391 --> 01:56:59,559
EVEN THOUGH IT REQUIRED A 

2423
01:56:59,559 --> 01:57:00,861
SPECIAL APPARATUS TO BE ABLE TO 

2424
01:57:00,861 --> 01:57:01,828
DO SO, HE WAS NOT GOING TO PASS 

2425
01:57:01,828 --> 01:57:11,972
THAT UP.

2426
01:57:15,208 --> 01:57:17,544
>> I'LL TELL YOU A STORY.

2427
01:57:17,544 --> 01:57:18,812
PHYSICIANS OFTEN GET CALLS FROM 

2428
01:57:18,812 --> 01:57:20,213
FRIENDS WHO HAVE FRIENDS WHO 

2429
01:57:20,213 --> 01:57:21,948
HAVE FRIENDS WHO NEED HELP.

2430
01:57:21,948 --> 01:57:24,551
THEY TRY TO GET THE BEST 

2431
01:57:24,551 --> 01:57:26,353
DOCTORS, WHO DO YOU RECOMMEND 

2432
01:57:26,353 --> 01:57:28,422
AND SO THIS HAPPENS A LOT AND WE

2433
01:57:28,422 --> 01:57:30,424
TAKE CALLS -- PHYSICIANS TAKE 

2434
01:57:30,424 --> 01:57:31,057
CALLS FROM ONE ANOTHER A LOT TO 

2435
01:57:31,057 --> 01:57:34,828
TRY TO HELP.

2436
01:57:34,828 --> 01:57:37,297
I GOT I CALL FROM A FRIEND WHO 

2437
01:57:37,297 --> 01:57:43,403
HAD A FRIEND WHOSE SON IS 11 AND

2438
01:57:43,403 --> 01:57:44,805
HAS SOMETHING COMPLETELY 

2439
01:57:44,805 --> 01:57:47,007
DIFFERENT FROM PROGERIA BUT HAS 

2440
01:57:47,007 --> 01:57:49,676
HAD IT SINCE BIRTH AND NEEDED A 

2441
01:57:49,676 --> 01:57:53,847
SURGERY, NEUROLOGIC TYPE OF 

2442
01:57:53,847 --> 01:57:56,082
SURGERY AND THEY WERE NOT FROM 

2443
01:57:56,082 --> 01:57:58,852
MASSACHUSETTS AND LOOKING 

2444
01:57:58,852 --> 01:57:59,686
LOCALLY AND WANTED TO GET MY 

2445
01:57:59,686 --> 01:58:03,023
THOUGHTS ON WHO WOULD BE GREAT 

2446
01:58:03,023 --> 01:58:04,057
EITHER AT BOSTON CHILDREN'S OR 

2447
01:58:04,057 --> 01:58:04,591
SOME PLACE ELSE.

2448
01:58:04,591 --> 01:58:05,792
I WAS TRYING TO HELP WITH THAT 

2449
01:58:05,792 --> 01:58:08,395
AND TALKING TO MY COLLEAGUES.

2450
01:58:08,395 --> 01:58:11,331
SO I SPOKE TO THIS MOM AND SHE 

2451
01:58:11,331 --> 01:58:14,634
TOLD ME A STORY THAT I WAS JUST 

2452
01:58:14,634 --> 01:58:15,168
STUNNED BY.

2453
01:58:15,168 --> 01:58:17,637
THIS IS A COMPLETELY DIFFERENT 

2454
01:58:17,637 --> 01:58:19,506
DISEASE PROCESS AND SHE SAID, 

2455
01:58:19,506 --> 01:58:25,312
YOU KNOW, WHEN MY SON WAS BORN 

2456
01:58:25,312 --> 01:58:28,048
YOUR SON'S TED TALK WAS WHAT GOT

2457
01:58:28,048 --> 01:58:29,850
US THROUGH.

2458
01:58:29,850 --> 01:58:32,819
WE WERE SO INSPIRED BY WHAT -- 

2459
01:58:32,819 --> 01:58:34,955
WE WERE SO DEVASTATED GOING 

2460
01:58:34,955 --> 01:58:37,057
THROUGH SO MUCH AND WATCHED 

2461
01:58:37,057 --> 01:58:39,125
SAM'S TED TALK AND GOT US 

2462
01:58:39,125 --> 01:58:40,126
THROUGH AND COULD NOT BELIEVE I 

2463
01:58:40,126 --> 01:58:44,598
WAS TALKING TO SAM'S MOM.

2464
01:58:44,598 --> 01:58:47,033
SOMEBODY SAID TALK TO LESLIE 

2465
01:58:47,033 --> 01:58:48,068
GORDON AND CHAT WITH HER AND 

2466
01:58:48,068 --> 01:58:49,569
TELL HER WHAT YOU NEED.

2467
01:58:49,569 --> 01:58:51,538
I WAS SO IMPACTED BY THAT 

2468
01:58:51,538 --> 01:58:58,678
BECAUSE IT'S A RIPPLE AFFECT.

2469
01:58:58,678 --> 01:59:04,217
WE'VE BEEN TALKING ABOUT A 

2470
01:59:04,217 --> 01:59:06,520
RIPPLE EFFECT AND WE GET THAT 

2471
01:59:06,520 --> 01:59:10,590
TOO BUT JUST HIS RIPPLE AFFECTS,

2472
01:59:10,590 --> 01:59:13,560
I CAN'T IMAGINE IF IT REACHED 

2473
01:59:13,560 --> 01:59:15,595
THAT WOMAN AND THAT FAMILY, WHO 

2474
01:59:15,595 --> 01:59:17,430
ELSE HAS IT REACHED AND WHAT 

2475
01:59:17,430 --> 01:59:21,535
ELSE HAS SAM DONE FOR THEM?

2476
01:59:21,535 --> 01:59:22,936
THAT MADE ME FEEL REALLY GOOD.

2477
01:59:22,936 --> 01:59:25,572
>> WE HAVE REACHED THE END
OF 

2478
01:59:25,572 --> 01:59:28,408
OUR TIME BUT I THINK ON BEHALF 

2479
01:59:28,408 --> 01:59:29,843
OF EVERYONE HERE AND THE LARGE 

2480
01:59:29,843 --> 01:59:31,578
NUMBER OF PEOPLE WHO HAVE 

2481
01:59:31,578 --> 01:59:34,681
WATCHED AND WILL GO TO THE 

2482
01:59:34,681 --> 01:59:37,284
ARCHIVE, WE CAN HARDLY THANK YOU

2483
01:59:37,284 --> 01:59:40,120
ENOUGH FOR NOT ONLY AN 

2484
01:59:40,120 --> 01:59:43,189
INCREDIBLY CONCISE AND BEAUTIFUL

2485
01:59:43,189 --> 01:59:45,125
PRESENTATIONS BUT REALLY 

2486
01:59:45,125 --> 01:59:49,563
EMPHASIZING THE IMPORTANCE OF 

2487
01:59:49,563 --> 01:59:55,936
THESE RARE DISEASES AND THE 

2488
01:59:55,936 --> 01:59:57,671
STRUGGLE THAT'S INVOLVED TO 

2489
01:59:57,671 --> 01:59:59,773
BRING SOME RELIEF TO THESE 

2490
01:59:59,773 --> 02:00:05,645
PATIENTS IF NOT CURE, AND 

2491
02:00:05,645 --> 02:00:06,846
ENORMOUS EFFORT THAT'S REQUIRED 

2492
02:00:06,846 --> 02:00:09,249
WHICH YOUR ORGANIZATION AND THE 

2493
02:00:09,249 --> 02:00:11,451
FOUNDATION COUPLED WITH THE 

2494
02:00:11,451 --> 02:00:14,054
RESEARCH EFFORTS AND NOW IT 

2495
02:00:14,054 --> 02:00:15,689
BECOMES A WORLD ACTIVITY.

2496
02:00:15,689 --> 02:00:17,324
ONE ONLY HOPES THIS WILL CARRY 

2497
02:00:17,324 --> 02:00:23,463
ON IN SOME WAY TO MANY OF THE 

2498
02:00:23,463 --> 02:00:24,931
7,000 RARE DISEASES MOST OF 

2499
02:00:24,931 --> 02:00:28,234
WHICH ARE DEVASTATING SO THANK 

2500
02:00:28,234 --> 02:00:28,401
YOU.

2501
02:00:28,401 --> 02:00:29,269
THANK YOU VERY VERY MUCH FOR THE

2502
02:00:29,269 --> 02:00:31,838
MOST EXCITING AFTERNOON.

2503
02:00:31,838 --> 02:00:34,074
>> THANKS FOR INVITING US.

2504
02:00:34,074 --> 02:00:34,808
>> THANKS, EVERYBODY.

2505
02:00:34,808 --> 02:00:35,141
THANKS, SAMMY.

2506
02:00:35,141 --> 02:00:45,385
>> THANK YOU.