Demystifying Medicine Lecture Series

Although the fundamental molecular pathophysiology of sickle cell anemia was elucidated in studies of this genetic disease starting more than 70 years ago, it is only in about the last two decades that this knowledge has led to specific therapies. Indeed in the last decade serious attention has turned to the possibility of a genetic cure of this condition.

Have we finally cured sickle cell anemia? Not quite, but we may be on the cusp. Really. In a dozen clinical trials planned or underway, some at the NIH Clinical Center, researchers are applying gene therapy to cure this well-studied genetic disorder that causes agonizing pain attacks, stroke, and early death.

Sickle cell anemia (SCA) is the most common manifestation of sickle cell disease (SCD), which is caused by a single gene mutation on chromosome 11 inherited from both of one's parents. The mutation results in the periodic creation of sickle hemoglobin (HbS), as opposed to normal hemoglobin (HbA). The HbS distorts the shape of round blood cell into a sickle, which impedes the flow of cells, particularly in narrow vessels, and prevents oxygen from reaching tissues.

More than 4.4 million people have SCD worldwide, including about 100,000 in the United States, mostly of African descent. Treatment is complicated by inadequate and inequitable access to health care.

Our first speaker is Alan Schechter, chief of NIDDK's Molecular Medicine Branch. Dr. Schechter will discuss an overview of the current understanding of these pathophysiological processes, from genes to the vascular bed, and how this knowledge has led to FDA approval of four agents for therapy and has resulted in the current study of hundreds of other potential therapeutic agents. His research focuses on the interaction of the signaling molecule nitric oxide (NO) and hemoglobin, with the goal of understanding how NO may be transported by blood and thus act at distal sites, opening up its use as a pharmacological agent. This work has the potential for developing therapies for a variety of ischemic diseases, as well as sickle cell anemia and related hemoglobinopathies in which blood flow is impaired.

Our second speaker is John Tisdale, a senior investigator in the NHLBI Molecular and Clinical Hematology Section. Dr. Tisdale will review the two classes of therapies – allogeneic bone marrow transplantation and gene addition or correction – that have the potential to cure individuals, but have significant barriers to general applicability to the population with this disease, especially in low resource countries where it is so prevalent. Tisdale works on strategies to cure sickle cell disease by replacing the bone marrow cells that give rise to sickled red blood cells with bone marrow cells from a donor who does not have the disease. This transplantation strategy has shown remarkable results in children and young adults with the disease. Tisdale also is leading a multi-center nationwide study to test the effects of an experimental gene therapy protocol for sickle cell disease.

Together, the speakers will elucidate how the NIH hopes to develop both treatments and cures for sickle cell disease.

For more information go to https://demystifyingmedicine.od.nih.gov