Experimental Gene Therapy Could Cure Sickle Cell Disease
/By Pat Anson, PNN Editor
Experimental gene therapy is helping sickle cell patients develop normal red blood cells and could potentially be a cure for the disease, according to research recently published in The New England Journal of Medicine.
In early-stage Phase 1 and 2 clinical trials at the University of Alabama at Birmingham, 25 patients treated with a gene therapy called LentiGlobin produced stable amounts of red blood cells containing hemoglobin after a single infusion.
Sickle cell disease is a genetic disorder that causes red blood cells to form in a crescent or sickle shape, which creates painful blockages in blood vessels that can lead to anemia, infections, strokes and organ failure. About 100,000 Americans live with sickle cell disease, primarily people of African or Hispanic descent.
Unlike other gene therapies that edit or silence genes, LentiGlobin adds a modified gene that reprograms the diseased blood cells.
“In this therapy, we do not change or edit the gene that causes sickle cell disease,” says Julie Kanter, MD, director of the UAB Adult Sickle Cell Clinic. “Instead, we use a viral vector to deliver a new gene that will make a healthy hemoglobin — a beta hemoglobin — into the stem cell. This is like coding new instructions into the cell.”
The new hemoglobin -- called HbAT87Q -- is slightly different from regular hemoglobin and is less likely to cause red blood cells to be misshaped. The HbAT87Q can also be measured more accurately inside the cell, allowing doctors to know how much of the new hemoglobin a patient is making on their own.
Although the gene therapy looks promising, researchers say more advanced studies are needed to make sure LentiGlobin is safe and effective long-term.
“In an earlier part of this study, we were not able to get enough of the new gene into each cell,” explained Kanter. This caused the blood cells to be stressed and for some patients to still have symptoms of sickle cell disease. Two patients in the initial group developed leukemia.
“We need to see that we have fixed this problem, says Kanter. “We also need to make sure this procedure both reduces pain/stops all pain crisis and prevents organ damage from sickle cell. This will take time. We will have to watch people for the next two to 15 years and measure their organ function compared to those who did not get this therapy.”
A 2020 report by the National Academies of Sciences, Engineering, and Medicine called for major changes in the way sickle cell disease is treated in the U.S. Compared to other chronic illnesses, stem cell disease has received little attention from the healthcare community, resulting in a lag in the development of new treatments.
Many stem cell patients also feel stigmatized when they have a pain flare and go to an emergency room, because ER staff are often ignorant about the disease and believe patients are seeking drugs.
“People with sickle cell disease have endured unnecessary hardship for more than 100 years. They have fewer medications and therapies than many other diseases and have received much less attention and funding. We need new and better options for people with sickle cell disease,” said Kanter.
Bone marrow and stem cell transplants are currently the only cures for sickle cell disease, but it’s often difficult to find good donors. Fewer than one in five people with the disease have compatible donors.
