Lentivirus-mediated gene therapy for Fabry disease Academic Article uri icon

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abstract

  • AbstractEnzyme 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.

authors

  • Khan, Aneal
  • Barber, Dwayne L
  • Huang, Ju
  • Rupar, C Anthony
  • Rip, Jack W
  • Auray-Blais, Christiane
  • Boutin, Michel
  • O’Hoski, Pamela
  • Gargulak, Kristy
  • McKillop, William M
  • Fraser, Graeme
  • Wasim, Syed
  • LeMoine, Kaye
  • Jelinski, Shelly
  • Chaudhry, Ahsan
  • Prokopishyn, Nicole
  • Morel, Chantal F
  • Couban, Stephen
  • Duggan, Peter R
  • Fowler, Daniel H
  • Keating, Armand
  • West, Michael L
  • Foley, Ronan
  • Medin, Jeffrey A

publication date

  • December 2021