UCLA gene therapy shows 95% success in ADA-SCID treatment

An experimental gene therapy developed by researchers at UCLA, University College London, and Great Ormond Street Hospital has reached a significant milestone in treating children with ADA-SCID, a rare and severe genetic immune disorder. A long-term study published in the New England Journal of Medicine indicates that the therapy successfully restored immune system function in 59 out of 62 children diagnosed with ADA-SCID. This disorder, caused by mutations in the ADA gene, results in severe combined immunodeficiency, making everyday activities dangerous due to the risk of life-threatening infections. Without treatment, children with ADA-SCID often do not survive beyond their second year of life.

The innovative gene therapy presents a promising alternative to traditional treatments, such as bone marrow transplants and weekly enzyme injections, which come with significant limitations and potential risks. The therapy involves harvesting a child's blood stem cells, essential for the production of blood and immune cells. Researchers then use a modified lentivirus to deliver a healthy copy of the ADA gene into these stem cells. Once reinfused into the patient, the corrected stem cells begin to generate healthy immune cells that can combat infections. While the initial production of immune cells occurs shortly after treatment, it may take six to twelve months for the immune system to fully recover to normal levels.

The study, led by Dr. Donald Kohn of UCLA, emphasizes the long-term outcomes for patients treated between 2012 and 2019, demonstrating the therapy's effectiveness over time. In this extensive study, which includes 474 total patient-years of follow-up, the results show that immune function in the 59 successfully treated patients has remained stable beyond the initial recovery period. Importantly, no serious complications were reported, reinforcing the safety and durability of this gene therapy approach. Dr. Kohn expressed optimism about the findings, noting that stability beyond the initial recovery phase is particularly encouraging. Most mild to moderate adverse events reported were related to routine preparatory procedures rather than the gene therapy itself.

For the three patients who did not achieve the desired immune function, they were able to revert to existing standard-of-care treatments, with two undergoing bone marrow transplants and one receiving enzyme injections while awaiting a transplant. The study also highlights a crucial advancement in the accessibility of this gene therapy. More than half of the treated children received a frozen preparation of corrected stem cells, which delivered outcomes comparable to those who received fresh stem cells. This cryopreservation method enhances the therapy's accessibility by allowing stem cells to be collected locally, processed elsewhere, and then shipped back to nearby hospitals. According to Dr. Katelyn Masiuk, one of the co-authors, this method eliminates the need for families to travel long distances to specialized treatment centers.

Moreover, the freezing process allows for thorough testing and quality control before treatment, ensuring accurate dosing of the conditioning chemotherapy. Looking ahead, the UCLA team, with support from the California Institute for Regenerative Medicine, is actively pursuing FDA approval for this groundbreaking gene therapy. Rarity PBC, a public benefit corporation formed by alumni from Dr. Kohn's lab, has licensed the therapy and is collaborating with commercial manufacturers to produce it under pharmaceutical-grade conditions. Dr. Kohn aims to achieve FDA approval within the next two to three years, marking a significant step forward in the treatment of ADA-SCID and potentially paving the way for similar therapies targeting other genetic disorders.