In an invited letter to the journal of Clinical and Translational Discovery, Dr. Rina Kansal describes some of the history behind Fabry disease and reveals the positive impact that current standard-of-care therapies.  Yet, because current therapies are leaving some symptoms poorly addressed, Dr. Kansal goes on to describe the promise of cell therapy for addressing the unmet needs that remain for Fabry patients (https://doi.org/10.1002/ctd2.70042). 

Dr. Rina Kansal, MD, is a Director in Medical Oncology at the Versiti Blood Center of Wisconsin. She recently was lead editor in the publication of “Precision Medicine - Where Are We And Where Are We Going?” (https://doi.org/10.52305/WQEQ5178) - a 500+ page book that provides a comprehensive perspective on emerging diagnostics and therapeutics. In her review of the therapeutic outcome of the Glafabra team’s FACTS trial, Dr Kansal takes us on a journey that outlines how genetic disease of Fabry disease occurs by causing loss-of-gene-function in lipid metabolism.

She then describes how the loss of this enzyme leads to build up of toxic metabolites that lead to progressive damage to various tissues in the body.

Next, she describes how our cell therapy works in patients, where we use a lentivirus to insert a functional enzyme into the patient's own cells.  The resulting modified cells are put back into the patient where they diffuse broadly and help restore enzyme function to neighboring cells by providing cross-correction.

Dr. Kansal noted the trial data showed significant drops in toxic metabolites.  However, more studies are needed because: 

“The trial was designed as a safety study and was not adequately powered to investigate correlations between gene therapy and specific clinical parameters.”

She also noted that:

“After haematologic malignancies have occurred in patients in a gene therapy trial for another disease, the investigators performed additional experiments to study viral integration sites following gene therapy. These studies provided evidence for persistent polyclonal haematopoiesis and no evidence of clonal dominance in any patient”  - (https://pmc.ncbi.nlm.nih.gov/articles/PMC9932294/)

As a result, these pilot studies done in Canada by some of the founders and advisors in Glafabra have significantly derisked the Fabry asset for any cancer concerns.

With Glafabra's cell therapy, safety appears to be evident and the data is showing tantalizing evidence of efficacy. It now becomes important for us to do a repeat study on a larger cohort of patients. This will allow the data to be sufficiently empowered and provide multiple lines of evidence of the cell therapies effectiveness in treating Fabry disease.