Enrollment began in 2017 for a groundbreaking clinical trial that is testing gene transfer therapy as a potential cure for sickle cell disease. The study will evaluate a patented treatment developed at Cincinnati Children’s by pediatric hematologist Punam Malik, MD, principal investigator of the trial and the director of the Cincinnati Comprehensive Sickle Cell Center.

Malik’s innovation flows from observations that enforcing fetal hemoglobin (HbF) expression in adult red blood cells prevents red blood cell sickling when present in sufficient quantity. For most people, HbF turns off soon after birth, and their bodies begin producing adult hemoglobin (HbA). But children with the sickle cell mutation instead begin to produce a defective form of adult hemoglobin, hemoglobin S (HbS). HbS causes red blood cells to take on the sickle shape that is characteristic of the disease.

However, some adults never stop producing HbF – and when those adults have sickle cell disease, their symptoms are mild. Malik and her team developed a vector with an HbF-producing gene and modified it so that its “on” switch remains permanently flipped, counteracting the sickle hemoglobin and preventing sickling. They also manipulated the gene so that it preferentially forms HbF in the presence of HbS.

Malik and her team proved several years ago that the vector reactivates HbF and halts blood cell sickling in mice and in human tissue samples. The clinical trial involves collecting the patient’s bone marrow stem cells using a lentivirus vector to deliver an HbF gene to the cells, and then returning the engineered cells to the patient where they may produce normal red blood cells instead of the sickle-shaped cells. A recent collaboration with the University of West Indies has increased referrals to the study. So far, two adults have been recruited to the study, and enrollment is still open. If the therapy is found to be safe and effective in adults, Malik says she will extend the study to children.

“If we are effective at replicating what we did in lab, we are looking at a cure for a disease that affects more than 100,000 people in the United States and millions of people worldwide,” Malik says. “The therapy also may serve as a treatment for thalassemia. Even if is not curative, perhaps it will lessen the intensity of these diseases.”

The study expenses are supported by funding from the National Institutes of Health and the Doris Duke Charitable Foundation.