Physician researcher from UH Rainbow Babies & Children’s co-authors two studies published in the New England Journal of Medicine

CLEVELAND - Jignesh Dalal, MD, Director of Pediatric Cell Therapy and Bone Marrow Transplant at UH Rainbow Babies & Children's Hospital and the Mary Ann Cross Chair in Pediatric and Young Adult Immunotherapy, is a co-author on two newly published studies in the New England Journal of Medicine that report encouraging early results from separate investigational gene therapy trials for sickle cell disease (SCD).

The studies add to growing evidence that gene editing may offer a new approach for patients with severe SCD, a painful inherited blood disorder that causes chronic hemolytic anemia and recurrent vaso-occlusive crises. The findings also highlight UH Rainbow's role as an academic partner in advancing promising cell and gene therapies through collaboration with leading biopharmaceutical companies.

"One of the most important aspects of this research is that it moves us closer to therapies more than a century after initial description of sickle cell disease," said Dr. Dalal. "These studies reflect the promise of gene editing and may meaningfully change the course of treatment and quality of life for patients and their families."

In one study, researchers evaluated ristoglogene autogetemcel (risto-cel), an investigational base-edited therapy designed to reduce the effects of sickle hemoglobin by increasing production of fetal hemoglobin. In the Phase 1/2 study, 31 patients received risto-cel after myeloablative conditioning with busulfan. The therapy was associated with rapid engraftment, durable increases in fetal hemoglobin, and no investigator-reported severe vaso-occlusive crises occurring later than 60 days after the final red-cell transfusion.

In the second study, investigators evaluated renizgamglogene autogedtemcel (reni-cel), an investigational CRISPR-Cas12a gene-edited autologous stem-cell therapy designed to reactivate fetal hemoglobin production. Among 28 patients treated, the therapy led to successful engraftment, increased total hemoglobin and fetal hemoglobin levels, and no vaso-occlusive events in 27 of 28 patients after infusion.

"These findings are encouraging because they suggest that gene editing may help address the underlying biology of sickle cell disease rather than only treating its symptoms," said Dr. Dalal. "Further study will be important, but this work represents a significant step forward for patients and families affected by this condition."

Results from both clinical trials are preliminary, and additional research will be needed to better understand long-term safety, durability and access. Still, the results provide important momentum for ongoing efforts to develop transformative treatments for SCD.

The risto-cel study was funded by Beam Therapeutics and the reni-cel study was funded by Editas Medicine. Both studies were published in the New England Journal of Medicine:

Base Editing of HBG1 and HBG2 Promoters for Sickle Cell Disease
https://www.nejm.org/doi/full/10.1056/NEJMoa2504835

CRISPR-Cas12a Gene Editing of HBG1 and HBG2 Promoters to Treat Sickle Cell Disease
https://www.nejm.org/doi/full/10.1056/NEJMoa2415550