Innovative Gene Therapy Trial Shows Promise for Fabry Disease Treatment

A recent study has revealed groundbreaking findings from a gene therapy trial aimed at treating classical Fabry disease, indicating a significant advancement in addressing this rare genetic condition. The trial, known as the FACTs (Fabry Disease Clinical Research and Therapeutics) study, was conducted across various locations in Canada, including Halifax, Toronto, and Calgary, and commenced in 2016.

The research involved five male participants who received a novel lentivirus (LV)-mediated gene therapy designed to enable their bodies to produce the missing enzyme responsible for Fabry disease. The findings have been published in the journal Clinical and Translational Medicine.

The results of the trial have been described as life-altering; four out of the five participants demonstrated notable improvements in their biomarkers, and three of them were able to completely discontinue their enzyme replacement therapy (ERT). This raises the possibility of a single, definitive treatment for the condition.

According to Dr. Michael West, a nephrologist at the QEII Health Sciences Center and co-investigator of the trial, this study represents a crucial advancement in confirming the safety and efficacy of LV-mediated gene therapy for Fabry disease. The sustained positive response over five years has the potential to reshape the treatment landscape for patients affected by this condition, particularly with the option to discontinue ERT, which significantly improves quality of life.

Fabry disease leads to the accumulation of specific fat molecules in various tissues due to the body's inability to produce the correct form of an enzyme needed to break down these fatty substances. This accumulation can result in a range of severe symptoms, including pain in extremities, gastrointestinal issues, chronic fatigue, and serious complications such as kidney disease, heart failure, and strokes.

The innovative therapy utilizes engineered blood stem cells from the patients, which are modified to deliver a functional copy of the defective gene. Results from the trial indicated lasting enzyme production and stabilization of kidney function in one participant with advanced kidney disease. Notably, only two temporary severe adverse events were reported during the study, underscoring the therapy's favorable safety profile.

The study demonstrated that all five patients maintained a persistent presence of LV-marked blood cells and continuous enzyme production. Consequently, three patients were able to cease their biweekly ERT, leading to significant cost savings--approximately $3.7 million for provincial health-care programs.

One participant, who had not undergone ERT for four years, expressed that the experience significantly enriched his family life, highlighting the therapy's transformative potential.

Looking ahead, the research team aims to initiate a larger follow-up study involving 25 to 30 participants, including female patients, over a two to three-year period to further validate the findings and explore the therapy's broader applications.

For more detailed information, refer to the study published by Aneal Khan et al., titled Lentivirus-mediated gene therapy for Fabry disease: 5-year End-of-Study results from the Canadian FACTs trial in Clinical and Translational Medicine.