A study evaluating a pioneering lentivirus (LV)-mediated gene therapy trial for classical Fabry disease showed promising results over five years, indicating a potential breakthrough in treatment for the genetic disorder.
The trial, known as the FACTs (Fabry Disease Clinical Research and Therapeutics) study, was carried out in Halifax, Toronto and Calgary and started in 2016 with five Canadian men who were treated with a novel gene therapy that enabled their bodies to produce the missing enzyme that causes Fabry disease. The findings were published in the journal Clinical and Translational Medicine.
The results were life-changing: four of five patients showed significant biomarker improvements, and three were able to stop their enzyme replacement therapy (ERT) entirely, suggesting the possibility of a “one-and-done” treatment.
“This trial marks a critical step forward in demonstrating the safety and efficacy of LV-mediated gene therapy for Fabry disease,” says Dr. Michael West, a Dal professor and nephrologist at the QEII Health Sciences Center, who was a co-investigator in the study that was the first gene therapy trial for Fabry.
The study revealed that all five patients had sustained persistence of LV-marked blood cells and continual enzyme production. As a result, three patients could stop biweekly ERT (every two weeks), with a saving of roughly $3.7 million in costs for provincial health-care programs.
Dr. West said the goal now is to create a similar study with 25 to 30 patients, including women, over a two- to three-year period.
Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal α-galactosidase A, and the subsequent accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Males with classical Fabry disease develop early symptoms including pain and hypohidrosis by the second decade of life reflecting disease progression in the peripheral and autonomic nervous systems. An insidious cascade of disease processes ultimately results in severe renal, cardiac, and central nervous system complications in adulthood. The late complications are the main cause of late morbidity, as well as premature mortality. Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic.
Detailed knowledge of the natural history of Fabry disease provides the basis to measure the effects of treatment options. Several registries of clinical data are currently active for Fabry disease, of which the Fabry Registry (www.fabryregistry.com) is the largest. For the registries to provide aggregate data on natural history and treatment response for all participants, a relatively uniform practice standard would provide a useful framework. Moreover, as the overall care of Fabry patients moves beyond the realm of genetic subspecialists, there is a need for management guidelines for a rare condition in which there may be only a single patient per medical practice.
Source:
https://medicalxpress.com/news/2025-07-gene-therapy-trial-breakthrough-rare.html
https://www.alamy.com/gene-therapy-concept-vector-illustration-image382086162.html
https://www.nature.com/articles/gim200691
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