Longevity & AgingGene Therapy Replaces Daily Cysteamine in Rare Lysosomal Disease
A phase 1/2 trial at UC San Diego tested CTNS-RD-04, an ex vivo lentiviral gene therapy delivering functional CTNS cDNA into patients' own hematopoietic stem cells, in six adults with infantile cystinosis. After myeloablative conditioning with busulfan and infusion of gene-corrected CD34+ cells, all patients achieved sustained, polyclonal hematopoietic reconstitution. Over 29–63 months of follow-up, white blood cell cystine levels fell in five of six patients, CTNS expression rose 11–49-fold, and no monoclonal expansions or therapy-related malignancies occurred. Oral cysteamine—a burdensome regimen of up to 36 pills daily—was discontinued before infusion. Results suggest a single gene therapy treatment may reduce or replace lifelong cysteamine therapy while providing tissue-level cystine clearance conventional drugs cannot achieve.
