Experimental gene therapy approach for sickle cell shows promise for eliminating pain

Sickle-shaped red blood cells block blood vessels, causing severe pain and other medical problems.

An experimental gene therapy approach for treating sickle cell disease shows promise for eliminating painful crises that are associated with the condition, according to interim findings from a clinical trial. The treatment eliminated pain, one of the hallmarks of the disease, for at least three years in some patients, researchers said. 

The ongoing clinical trial, which is the largest of its kind to date and the first to report on long-term outcomes of the therapy, moves researchers closer to a cure for the debilitating and life-threatening disease. The study was published in the New England Journal of Medicine and presented simultaneously at the American Society of Hematology’s (ASH) annual meeting. 

Of 35 patients with severe sickle cell disease who were treated using an experimental gene therapy agent called LentiGlobin™, the treatment restored normal red blood cell function in all the patients, the researchers said. The patients produced normal amounts of red blood cells containing healthy hemoglobin, the molecule that carries oxygen to tissues, rather than unhealthy sickle-shaped hemoglobin.  Prior to receiving treatment, the patients experienced more than three severe pain episodes per year that required hospitalization. But after treatment, they did not experience any severe pain episodes. Researchers still do not know if the relief from pain will be lifelong.  

The treatment showed no severe side effects, including strokes, the researchers said. They hope that the treatment will prevent organ damage, including the kidneys, lungs, heart, and brain, that can result from long-term disease complications.  

“Data presented at ASH and published today in The New England Journal of Medicine affirm that this lentiviral gene transfer for sickle cell disease has the potential to improve the day-to-day reality of people living with sickle cell disease by eliminating the disruptive, painful crises that can occur multiple times per month,” said John F. Tisdale, M.D., corresponding author for the NEJM study and chief of the NHLBI’s Cellular and Molecular Therapeutics Branch.  

“Sickle cell is a complex and often misunderstood disease that is associated with more symptoms and long-term effects than pain alone,” Tisdale said. “It is encouraging to see that the treatment fundamentally impacted the pathophysiology of patients’ disease through the sustained production of vector-derived anti-sickling hemoglobin to substantially reduce sickling and hemolysis.”  
The NIH is one of 11 nationwide clinical trial sites involved in the gene therapy study. Under a Cooperative Research and Development Agreement (CRADA), the NHLBI is collaborating with Bluebird Bio using the company’s investigational agent LentiGlobin™ to explore the viability of gene therapies for sickle cell disease. The study was funded by Bluebird Bio.