Lentivirus-mediated gene therapy for Fabry disease.

Enzyme and chaperone therapies are used to treat Fabry disease. Such treatments are expensive and require intrusive biweekly infusions; they are also not particularly efficacious. In this pilot, single-arm study (NCT02800070), five adult males with Type 1 (classical) phenotype Fabry disease were infused with autologous lentivirus-transduced, CD34+-selected, hematopoietic stem/progenitor cells engineered to express alpha-galactosidase A (α-gal A). Safety and toxicity are the primary endpoints. The non-myeloablative preparative regimen consisted of intravenous melphalan. No serious adverse events (AEs) are attributable to the investigational product. All patients produced α-gal A to near normal levels within one week. Vector is detected in peripheral blood and bone marrow cells, plasma and leukocytes demonstrate α-gal A activity within or above the reference range, and reductions in plasma and urine globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) are seen. While the study and evaluations are still ongoing, the first patient is nearly three years post-infusion. Three patients have elected to discontinue enzyme therapy.

Citation

Aneal Khan, Dwayne L Barber, Ju Huang, C Anthony Rupar, Jack W Rip, Christiane Auray-Blais, Michel Boutin, Pamela O'Hoski, Kristy Gargulak, William M McKillop, Graeme Fraser, Syed Wasim, Kaye LeMoine, Shelly Jelinski, Ahsan Chaudhry, Nicole Prokopishyn, Chantal F Morel, Stephen Couban, Peter R Duggan, Daniel H Fowler, Armand Keating, Michael L West, Ronan Foley, Jeffrey A Medin. Lentivirus-mediated gene therapy for Fabry disease. Nature communications. 2021 Feb 25;12(1):1178

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PMID: 33633114

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