Gene therapy for SCID
Severe combined immunodeficiency (SCID) refers to a heterogeneous group of rare diseases in which both antibody-dependent and cellular immunity are severely impaired. About 15% of cases are due to adenosine deaminase (ADA) deficiency. Effective gene therapy for ADA deficiency has now been described in a multinational investigation.
Ten children with ADA-deficiency SCID and without a human leukocyte antigen (HLA)-identical sibling donor had nonmyeloablative conditioning with busulphan, followed by infusion of autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene. All 10 patients were alive after 1.8–8 years (median 4 years). The transduced stem cells have engrafted and turned into myeloid cells containing ADA and lymphoid cells. T-cell function became normal in nine patients, and eight are well without enzyme replacement therapy. Five patients discontinued immune globulin replacement therapy and produced antibodies in response to vaccines or viral antigens. Physical development improved and the patients developed clinical immunity to infections. Two patients had prolonged neutropenia; two had central-venous-catheter-related infections; and one each had hypertension, autoimmune hepatitis and reactivation of Epstein-Barr virus infection.
Gene therapy for this rare disease was safe and effective.
Ainti A, et al. Gene therapy for severe combined immunodeficiency due to adenosine deaminase deficiency. NEJM 2009;360:447–458; Kohn DB, Candotti F. Gene therapy fulfilling its promise. Ibid:518– 521 (editorial).