New Gene Correction Clinical Trial for Sickle Cell Disease Expanding to Children as Young as 12

The approach repairs the mutation in its original place, rather than working around it. The trial builds on decades of Stanford Medicine research.

Gene therapies have become a promising treatment option for some people with sickle cell disease. In sickle cell disease, one defective gene—the beta-globin gene—causes red blood cells to become sticky, firm, and sickle-shaped, instead of flexible and round. The sickle-shaped cells clump together. Blood can’t flow to tissues and organs and deliver oxygen, causing intense pain and organ damage.

Existing FDA-approved gene therapies for people with sickle cell disease work by increasing anti-sickling hemoglobin to stabilize the red blood cells. These therapies, Lyfgenia and Casgevy, are available at Lucile Packard Children’s Hospital Stanford.

A clinical trial testing a different gene editing approach, called gene correction, is currently available at Lucile Packard Children’s Hospital Stanford for adults 18 and older with severe sickle cell disease.

Damage from sickle cell disease accumulates from early childhood. Silent strokes and effects on learning and memory can begin in the first years of life, and organ damage builds over time. Opening the trial to younger participants is intended to intervene before more of that damage occurs. Starting this fall, the trial is expected to expand to include children as young as 12. Lucile Packard Children’s Hospital Stanford is currently one of six hospitals in the United States to offer this new therapy as part of the clinical trial, and the only hospital in Northern California.

The trial uses CRISPR gene editing to remove the faulty beta-globin gene and replace it with a copy of the gene that makes normal red blood cells. The trial, called Restore, is sponsored by Kamau Therapeutics. The Restore trial, registered on ClinicalTrials.gov as NCT04819841, is built on decades of Stanford Medicine research.

“Instead of adding a new gene or indirectly targeting the fetal hemoglobin pathway, but keeping the faulty gene as well, this new approach leaves patients with only working copies of the beta-globin gene,” said David Shyr, MD, a pediatric stem cell transplant specialist who is leading the Restore trial at Stanford. “We’re excited to see how this approach compares to existing gene therapies.”

Like FDA-approved gene therapies for sickle cell disease, Restore involves collecting a sample of each patient’s blood-forming stem cells, modifying them outside the patient’s body, and infusing them back into the patient.

If Restore is shown to be safe, future studies would be needed to test whether the approach is more effective than other gene therapies. Additional data from the Phase 1/2 trial are expected in the coming year.

“We’re proud to offer an array of treatment options for people with sickle cell disease,” said Tami John, MD, director of Clinical Gene Therapies for Stanford’s Bass Center for Childhood Cancer and Blood Diseases. “From disease-transformative FDA-approved gene therapies to cutting-edge clinical trials, to new approaches that make stem cell transplantation safer, to disease-modifying medications, we are here to support people with sickle cell disease from every angle.”

To learn more about gene therapies for sickle cell disease available at Lucile Packard Children’s Hospital Stanford, please email scgt_clinical_trials_office@lists.stanford.edu or call (650) 761-9001.