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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Gene therapy for immunodeficiency due to adenosine deaminase deficiency
New England Journal of Medicine, Volume 360, No. 5, Year 2009
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Description
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, 1.07×10 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. (ClinicalTrials.gov numbers, NCT00598481 and NCT00599781.) Copyright © 2009 Massachusetts Medical Society. All rights reserved.
Authors & Co-Authors
Aïuti, Alessandro
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Cattaneo, Federica
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Galimberti, Stefania
Italy, Milan
Università Degli Studi Di Milano-bicocca
Benninghoff, Ulrike
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Cassani, Barbara
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Callegaro, Luciano
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Scaramuzza, Samantha
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Andolfi, Grazia
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Mirolo, Massimiliano
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Brigida, Immacolata
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Tabucchi, Antonella
Italy, Siena
Università Degli Studi Di Siena
Carlucci, Filippo
Italy, Milan
Irccs Ospedale San Raffaele
Eibl, Martha Marianne
Austria, Vienna
Immunologische Tagesklinik
Aker, Mehmet
Israel, Jerusalem
Hadassah University Medical Centre
Slavin, Shimon
Israel, Jerusalem
Hadassah University Medical Centre
Al-Mousa, Hamoud A.
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Ghonaium, Abdulaziz Al
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Ferster, Alina
Belgium, Brussels
Hospital Universitaire Des Enfants Reine Fabiola
Duppenthaler, Andrea
Switzerland, Bern
University Children's Hospital, Bern
Notarangelo, Luigi Daniele
United States, Boston
Boston Children's Hospital
Wintergerst, Uwe
Germany, Munich
Klinikum Der Universität München
Buckley, Rebecca Hatcher
United States, Durham
Duke University Medical Center
Bregni, Marco
Italy, Milan
Ospedale San Giuseppe, Milano
Marktel, Sarah
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Valsecchi, Maria Grazia
Italy, Milan
Università Degli Studi Di Milano-bicocca
Rossi, Paolo
Italy, Rome
Università Degli Studi Di Roma Tor Vergata
Italy, Rome
Irccs Ospedale Pediatrico Bambino Gesù
Ciceri, Fabio
Italy, Siena
Università Degli Studi Di Siena
Minièro, Roberto
Italy, Turin
Università Degli Studi Di Torino
Bordignon, Claudio
Italy, Milan
Università Vita-salute San Raffaele
Italy, Milan
Molmed S.p.a.
Roncarolo, Maria Grazia
Italy, Milan
San Raffaele Telethon Institute for Gene Therapy
Italy, Milan
Università Vita-salute San Raffaele
Statistics
Citations: 924
Authors: 30
Affiliations: 18
Identifiers
Doi:
10.1056/NEJMoa0805817
ISSN:
00284793
e-ISSN:
15334406
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Noncommunicable Diseases
Study Design
Cohort Study