Gene therapy for immunodeficiency due to adenosine deaminase deficiency

Aiuti, Alessandro; Cattaneo, Federica; Galimberti, Stefania; Benninghoff, Ulrike; Cassani, Barbara; Callegaro, Luciano; Scaramuzza, Samantha; Andolfi, Grazia; Mirolo, Massimiliano; Brigida, Immacolata; Tabucchi, Antonella; Carlucci, Filippo; Eibl, Martha; Aker, Memet; Slavin, Shimon; Al-Mousa, Hamoud; Al Ghonaium, Abdulaziz; Ferster, Alina; Duppenthaler, Andrea; Notarangelo, Luigi; ... (2009). Gene therapy for immunodeficiency due to adenosine deaminase deficiency. New England journal of medicine NEJM, 360(5), pp. 447-58. Waltham, Mass.: Massachusetts Medical Society MMS 10.1056/NEJMoa0805817

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BACKGROUND: We investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. METHODS: We infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. RESULTS: All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA (mean range at 1 year in bone marrow lineages, 3.5 to 8.9%) and lymphoid cells (mean range in peripheral blood, 52.4 to 88.0%). Eight patients do not require enzyme-replacement therapy, their blood cells continue to express ADA, and they have no signs of defective detoxification of purine metabolites. Nine patients had immune reconstitution with increases in T-cell counts (median count at 3 years, 1.07x10(9) per liter) and normalization of T-cell function. In the five patients in whom intravenous immune globulin replacement was discontinued, antigen-specific antibody responses were elicited after exposure to vaccines or viral antigens. Effective protection against infections and improvement in physical development made a normal lifestyle possible. Serious adverse events included prolonged neutropenia (in two patients), hypertension (in one), central-venous-catheter-related infections (in two), Epstein-Barr virus reactivation (in one), and autoimmune hepatitis (in one). CONCLUSIONS: Gene therapy, combined with reduced-intensity conditioning, is a safe and effective treatment for SCID in patients with ADA deficiency. ( numbers, NCT00598481 and NCT00599781.)

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Duppenthaler, Andrea




Massachusetts Medical Society MMS




Anette van Dorland

Date Deposited:

04 Oct 2013 15:12

Last Modified:

20 Jul 2022 10:02

Publisher DOI:


PubMed ID:


Web of Science ID:


URI: (FactScience: 196578)

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