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

@article{citeulike:6081254, abstract = {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. 10.1126/science.1171242}, author = {Cartier, Nathalie and Hacein-Bey-Abina, Salima and Bartholomae, Cynthia C. and Veres, Gabor and Schmidt, Manfred and Kutschera, Ina and Vidaud, Michel and Abel, Ulrich and Dal-Cortivo, Liliane and Caccavelli, Laure and Mahlaoui, Nizar and Kiermer, Veronique and Mittelstaedt, Denice and Bellesme, Celine and Lahlou, Najiba and Lefrere, Francois and Blanche, Stephane and Audit, Muriel and Payen, Emmanuel and Leboulch, Philippe and l'Homme, Bruno and Bougneres, Pierre and Von Kalle, Christof and Fischer, Alain and Cavazzana-Calvo, Marina and Aubourg, Patrick}, citeulike-article-id = {6081254}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1171242}, citeulike-linkout-1 = {http://www.sciencemag.org/content/326/5954/818.abstract}, citeulike-linkout-2 = {http://www.sciencemag.org/content/326/5954/818.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19892975}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19892975}, day = {6}, doi = {10.1126/science.1171242}, journal = {Science}, keywords = {journalclub}, month = {November}, number = {5954}, pages = {818--823}, posted-at = {2009-11-06 16:38:28}, priority = {2}, title = {Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy}, url = {http://dx.doi.org/10.1126/science.1171242}, volume = {326}, year = {2009} }

TY - JOUR ID - citeulike:6081254 L3 - citeulike-article-id:6081254 N2 - 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. 10.1126/science.1171242 IS - 5954 JF - Science EP - 823 TI - Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy VL - 326 SP - 818 KW - journalclub AU - Cartier, Nathalie AU - Hacein-Bey-Abina, Salima AU - Bartholomae, Cynthia AU - Veres, Gabor AU - Schmidt, Manfred AU - Kutschera, Ina AU - Vidaud, Michel AU - Abel, Ulrich AU - Dal-Cortivo, Liliane AU - Caccavelli, Laure AU - Mahlaoui, Nizar AU - Kiermer, Veronique AU - Mittelstaedt, Denice AU - Bellesme, Celine AU - Lahlou, Najiba AU - Lefrere, Francois AU - Blanche, Stephane AU - Audit, Muriel AU - Payen, Emmanuel AU - Leboulch, Philippe AU - l'Homme, Bruno AU - Bougneres, Pierre AU - Von Kalle, Christof AU - Fischer, Alain AU - Cavazzana-Calvo, Marina AU - Aubourg, Patrick PY - 2009/11/06/ UR - http://dx.doi.org/10.1126/science.1171242 ER -