HSCI principal faculty member Stuart Orkin, M.D. is the recipient of the 2020 Harrington Prize for Innovation in Medicine. The award, established in 2014 by the Harrington Discovery Institute and the American Society for Clinical Investigation (ASCI), honors physician-scientists who have moved science forward with achievements notable for innovation, creativity and potential for clinical application.
Orkin is the David G. Nathan Distinguished Professor of Pediatrics at Harvard Medical School. He is being recognized for breakthrough discoveries about red blood cells that offer new treatments for patients with sickle cell disease and beta-thalassemia, which are among the most common genetic disorders.
Potential treatment for sickle cell disease
Sickle cell disease (SCD) occurs due to a genetic mutation in hemoglobin, the molecule in red blood cells that carries oxygen and delivers it to tissues. In SCD, normal disc-like red blood cells become rigid and sickle shaped due to abnormal polymerization of sickle hemoglobin. Red cells get stuck in small blood vessels, cutting off blood flow and leading to tissue damage and intense pain.
In SCD, the adult form of hemoglobin is affected — but a fetal form of hemoglobin, which is shut off shortly after birth, is normal. Orkin discovered how the switch between fetal and adult hemoglobin is controlled, solving a longstanding mystery and suggesting new ways to reactivate normal fetal hemoglobin. Specifically, Orkin showed that the gene BCL11A turns off fetal hemoglobin. By blocking BCL11A, fetal hemoglobin expression can be restored in the adult, offering a potential treatment.
At Boston Children’s Hospital, Orkin’s colleague David A. Williams has translated these findings to patients in a gene therapy trial where BCL11A expression is blocked. Dramatic clinical results in the first patients have validated BCL11A as a target for therapy. Promising preliminary findings of company-sponsored gene editing trials with BCL11A as a target have also been reported.
“The sickle cell community has been energized by this discovery, which is a complete game-changer for a large group of people living with SCD. Dr. Orkin’s work has paved the way for testing a gene therapy approach, and potentially other approaches, to treat this debilitating disease,” said W. Kimryn Rathmell, 2019–2020 President of the ASCI.
“Dr. Orkin is an extraordinary investigator and a dominant force in the fields of hematology and genetic disease. His discovery of BCL11A as a master regulator of hemoglobin gene switching, and his pursuit of application in sickle cell disease, is a prime example of how fundamental discovery can be leveraged for clinical impact,” said Jonathan S. Stamler, president of the Harrington Discovery Institute at University Hospitals in Cleveland, Ohio.
This story was originally published on the Harvard Gazette website on April 16, 2020, under the title “2020 Harrington Prize awarded for sickle cell disease research.”