Children’s Hospital Los Angeles joined a trial to investigate nula-cel, a gene-editing therapy designed to correct the sickle cell disease genetic mutation.
RT’s Three Key Takeaways:
- Direct Gene Modification: The investigational therapy, nula-cel, aims to address the root cause of sickle cell disease by directly modifying the beta-globin gene.
- Clinical Trial Expansion: While currently enrolling adults, the phase 1/2 RESTORE trial at Children’s Hospital Los Angeles plans to expand enrollment to children as young as 12 later this year.
- Distinct Therapeutic Approach: Unlike existing FDA approved treatments that alter hemoglobin production, this new method focuses on correcting the specific disease-causing mutation.
Children’s Hospital Los Angeles (CHLA) is one of three pediatric centers in the US participating in a phase 1/2 clinical trial to evaluate a new gene-editing approach for severe sickle cell disease, according to the hospital.
The study, called RESTORE, is evaluating the safety of an investigational therapy known as nula-cel. Sponsored by Kamau Therapeutics, the trial is currently enrolling adults 18 and older, with plans to expand enrollment to children as young as 12 later this year.
“One of the central questions in sickle cell gene therapy is whether directly modifying the beta-globin gene could ultimately help address the root cause of the disease,” said Ashley N Gray, site principal investigator and director of gene therapy for hemoglobinopathies in the Cancer and Blood Disease Institute at CHLA. “This study is an early step in exploring that question.”
The investigational method involves collecting a patient’s own blood-forming stem cells and modifying them outside the body before reinfusing them following chemotherapy. While the Food and Drug Administration (FDA) has approved other gene therapies like Casgevy and Lyfgenia, those treatments change how hemoglobin is produced without altering the underlying mutation. Nula-cel is designed to directly modify the beta-globin gene itself.
If the therapy is found to be safe, future research will be required to determine if the approach leads to clinical benefits, such as reducing the proportion of sickled red blood cells over time.
Thomas Coates, section head of hematology at CHLA and a physician-researcher, emphasized the importance of studying these therapies in younger populations to prevent long-term complications affecting the brain, bones, eyes, and kidneys.
“The majority of children in the US with sickle cell disease now survive into adulthood—but that doesn’t mean they’re well,” said Coates in a news release. “Gene therapy offers the potential to change the trajectory of disease before children develop long-term irreversible complications. The earlier we can safely treat patients, the better. That’s why research in pediatric populations is so critical.”
As gene-editing strategies continue to evolve, researchers aim to understand how new methods will fit into the healthcare landscape.
“As gene therapy becomes part of standard care, it’s just as important to rigorously study new approaches,” said Gray in a news release. “Our role is to offer today’s approved therapies while also helping to carefully evaluate future options for patients.”
