Lentivirus-mediated gene therapy for Fabry disease

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 and Jeffrey A. Medin ()
Additional contact information
Aneal Khan: University of Calgary
Dwayne L. Barber: University Health Network
Ju Huang: University Health Network
C. Anthony Rupar: Western University
Jack W. Rip: Western University
Christiane Auray-Blais: Université de Sherbrooke
Michel Boutin: Université de Sherbrooke
Pamela O’Hoski: McMaster University and Juravinski Hospital and Cancer Centre
Kristy Gargulak: Medical College of Wisconsin
William M. McKillop: Medical College of Wisconsin
Graeme Fraser: McMaster University and Juravinski Hospital and Cancer Centre
Syed Wasim: Princess Margaret Cancer Centre
Kaye LeMoine: Nova Scotia Fabry Disease Program
Shelly Jelinski: Alberta Children’s Hospital and Foothills Medical Centre
Ahsan Chaudhry: University of Calgary
Nicole Prokopishyn: University of Calgary
Chantal F. Morel: University Health Network
Stephen Couban: Dalhousie University
Peter R. Duggan: University of Calgary
Daniel H. Fowler: Rapa Therapeutics
Armand Keating: University Health Network
Michael L. West: Dalhousie University
Ronan Foley: McMaster University and Juravinski Hospital and Cancer Centre
Jeffrey A. Medin: University Health Network

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-21371-5

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