Hematopoietic Stem-Cell Gene Therapy for Cystinosis

BACKGROUND: , the gene encoding cystinosin, a lysosomal transmembrane cystine transporter. In patients with cystinosis, cystine accumulates within lysosomes in all organs. The cystine-depleting agent cysteamine delays but does not prevent disease progression. METHODS: complementary DNA, in patients with cystinosis. The primary end points were the safety and the side-effect profiles of CTNS-RD-04. Secondary end points were measures of efficacy, including white-cell cystine levels and cystine storage depletion. Oral cysteamine was withdrawn before CTNS-RD-04 infusion, and cysteamine eyedrops were withdrawn 1 month after myeloablation. RESULTS: CD34+ cells per kilogram of body weight, and vector copy numbers ranged from 0.59 to 2.91 copies per diploid genome. All the patients had sustained and highly polyclonal hematopoietic reconstitution; vector copy numbers at 24 months ranged from 0.51 to 2.67 copies per diploid genome. A total of 217 adverse events occurred, most of which were mild or moderate in severity and largely consistent with the procedures and underlying disease. No evidence of monoclonal expansion was noted. White-cell cystine levels decreased from baseline except in Patient 4, who had the lowest vector copy number. CONCLUSIONS: In this small study, CTNS-RD-04, an ex vivo gene therapy for cystinosis, had adverse effects that were largely consistent with the myeloablative regimen and underlying disease profile. White-cell cystine levels decreased after therapy. (Funded by the California Institute for Regenerative Medicine and others; ClinicalTrials.gov number, NCT03897361.).