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.

Regulatory Framework for Conducting Clinical Research in Canada.

Research in human subjects is at the core of achieving improvements in health outcomes. For clinical trials, in addition to the peer review of the results before publication, it is equally important to consider whether the trial will be conducted in a manner that generates data of the highest quality and provides a measure of safety for the participating subjects. In Canada, there is no definitive legislation that governs the conduct of research involving human subjects, but a network of regulations at different levels does provide a framework for both principal investigators and sponsors. In this paper, we provide an overview of the federal, provincial and institutional legislation, guidelines and policies that will inform readers about the requirements for clinical trial research. This includes a review of the role of the Food and Drug Regulations under the Food and Drugs Act and the Tri-Council Policy Statement (TCPS2), an overview of provincial legislation across the country, and a focus on selected policies from institutional research ethics boards and public health agencies. Many researchers may find navigation through regulations frustrating, and there is a paucity of information that explains the interrelationship between the different regulatory agencies in Canada. Better understanding the process, we feel, will facilitate investigators interested in clinical trials and also enhance the long-term health of Canadians.