A gene-edited treatment for severe sickle cell disease showed encouraging results in a recent clinical trial, according to findings published on Apr. 1 in the New England Journal of Medicine. The RUBY Trial reported that 27 out of 28 patients experienced no painful sickle cell crises after receiving the experimental therapy, which researchers described as a "functional cure."
Sickle cell disease is a genetic disorder that causes red blood cells to become misshapen and block blood flow, leading to pain and organ complications. Current curative options are limited and often involve bone marrow transplants with significant risks.
The new approach uses Renizgamglogene autogedtemcel (reni-cel), an experimental one-time gene editing therapy that modifies a patient's own stem cells to correct the mutation responsible for the disease. The therapy increases levels of fetal hemoglobin, preventing red blood cells from taking on the abnormal sickle shape and improving overall hemoglobin levels.
"We have seen that a benefit of this CRISPR/Cas12a gene-editing technology is that there is no rejection, so it's different from traditional bone marrow transplants, which is standard treatment for sickle cell patients currently," said Rabi Hanna, M.D., lead author and chair of Pediatric Hematology – Oncology & Blood and Bone Marrow Transplant Division at Cleveland Clinic Children's. "Our aim has been to achieve a functional cure to help prevent any future damage caused by sickle cell disease, and these latest results are compelling."
The trial involved collecting stem cells from each patient for gene editing before administering chemotherapy to clear their bone marrow. The repaired cells were then infused back into their bodies. Most patients saw key blood cells recover within one month after treatment; by six months, average total hemoglobin levels increased from 9.8 g/dL before treatment to 13.8 g/dL—a level similar to individuals without the disorder—while fetal hemoglobin averaged 48.1%.
Cleveland Clinic provides specialized care for adults and children with sickle cell disease through comprehensive services beginning in childhood.
The RUBY Trial was sponsored by Editas Medicine.
