Journal
SCIENCE
Volume 326, Issue 5954, Pages 818-823Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1171242
Keywords
-
Categories
Funding
- INSERM
- European Leukodystrophy Association
- Association Francaise contre les Myopathies
- La Fondation de France
- STOP-ALD foundation
- La Fondation Avenir
- Etablissement Francais des Greffes
- Thermo Fisher Scientific
- 6th Framework European Economic Community ( EEC) Programme [LSHM-CT2004-502987]
- Programme Hospitalier de Recherche Clinique [AOM 3043]
- Assistance Publique-H pitaux de Paris
- Centre d' Investigation Clinique-Biotherapy, and Association Fran aise contre les Myopathies
- Deutsche Forschungsgemeinschaft [SPP 1230]
- German Ministry of Education and Research (TREATID)
- Helmholtz Association
- 6th Framework EEC Programme (CONSERT, CLINIGENE)
Ask authors/readers for more resources
X-linked adrenoleukodystrophy (ALD) is a severe brain demyelinating disease in boys that is caused by a deficiency in ALD protein, an adenosine triphosphate-binding cassette transporter encoded by the ABCD1 gene. ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT). We initiated a gene therapy trial in two ALD patients for whom there were no matched donors. Autologous CD34(+) cells were removed from the patients, genetically corrected ex vivo with a lentiviral vector encoding wild-type ABCD1, and then re-infused into the patients after they had received myeloablative treatment. Over a span of 24 to 30 months of follow-up, we detected polyclonal reconstitution, with 9 to 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein. These results strongly suggest that hematopoietic stem cells were transduced in the patients. Beginning 14 to 16 months after infusion of the genetically corrected cells, progressive cerebral demyelination in the two patients stopped, a clinical outcome comparable to that achieved by allogeneic HCT. Thus, lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in ALD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available