Until now, gene therapy for a severe immune system disorder has only succeeded in infants, but a small clinical trial shows that it can also treat older children and young adults. The treatment restored normal immune function in some patients for at least two to three years, offering new hope for older patients with X-linked severe combined immune deficiency (SCID-X1).
The abnormally low levels of adaptive immune cells in SCID-X1 patients, who are mostly male, are caused by mutations in a gene that encodes part of a receptor critical for immune function. Gene therapy correcting this gene in patients’ hematopoietic or blood-forming stem cells can help restore healthy immune cells in infants, but often fails in older children.
Suk See De Ravin and colleagues tested a lentiviral gene therapy in five SCID-X1 patients aged seven to 23, who continued to have immune problems despite previous hematopoietic stem cell transplantation. After treatment, the patients displayed gene-corrected T, B, and natural killer cells, partially restoring normal protective immune responses. Clinical symptoms such as chronic norovirus infection and a viral skin condition also markedly improved in some patients. These benefits persisted for six to nine months after treatment in three younger patients and, notably, for two to three years in two older patients.
The results suggest that gene therapy can offer long-term benefits for older patients with SCID-X1.