DOI: 10.1126/science.1171242 ISSN:

Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy

Nathalie Cartier, Salima Hacein-Bey-Abina, Cynthia C. Bartholomae, Gabor Veres, Manfred Schmidt, Ina Kutschera, Michel Vidaud, Ulrich Abel, Liliane Dal-Cortivo, Laure Caccavelli, Nizar Mahlaoui, Véronique Kiermer, Denice Mittelstaedt, Céline Bellesme, Najiba Lahlou, François Lefrère, Stéphane Blanche, Muriel Audit, Emmanuel Payen, Philippe Leboulch, Bruno l’Homme, Pierre Bougnères, Christof Von Kalle, Alain Fischer, Marina Cavazzana-Calvo, Patrick Aubourg
  • Multidisciplinary
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Slowing Brain Disease with Gene Therapy

X-linked adrenoleukodystrophy (ALD), the hereditary brain demyelinating disorder that was featured in the movie “ Lorenzo's Oil ,” is typically treated by transplantation of bone marrow from matched donors. This treatment slows progression of the disease by introducing cells that differentiate into myelin-producing cells. Cartier et al. (p. 818 ; see Perspective by Naldini ) tested an alternative gene therapy–based approach in two young patients without matched donors. A lentiviral vector was used to introduce a wild-type copy of the ALD gene into the patients' hematopoietic stem cells ex vivo. The modified cells were then infused back into the patients. Expression of the transferred gene was still detectable in the patients' blood cells 2 years later, and both patients showed neurological improvement and a delay in disease progression comparable to that seen with bone marrow transplants.

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