Experimental Gene Therapy Shows Promise Treating Fabry Disease

According to a publication from Fabry Disease News, biotechnology company Avrobio recently announced that early phase 1 and 2 clinical studies of experimental Fabry treatment AVR-RD-01 have yielded encouraging results.

Although only a few patients have been enrolled in the AVR-RD-01 studies thus far, many of them have shown improvement greater than that normally seen in the Fabry disease standard of treatment, which involves regular enzyme replacement therapy.

About Fabry Disease

Fabry disease is a rare, genetically-inherited condition characterized by the progressive buildup of globotriaosylceramide in cells throughout the body. Globotriaosylceramide is a kind of fat that is normally broken down in the lysosomes (sacks of digestive enzymes found in almost every animal cell), but people with Fabry disease can’t properly break these fat molecules down.

Fabry disease is caused by mutations to a gene called GLA. In otherwise healthy individuals, GLA codes for the production of alpha-galactosidase A — an enzyme that binds to and breaks down globotriaosylceramide. However, mutations to GLA can instead lead to the production of mutant alpha-galactosidase A that is inefficient or outright incapable of breaking down its target molecule.

Because the build-up of globotriaosylceramide occurs gradually over time, individuals born with Fabry disease may not show any symptoms at birth. However, system-wide signs and symptoms may become apparent in early childhood.

In severe cases, fatal complications can arise. Severe kidney damage, stroke, and even cardiac arrest can occur as a result of the globotriaosylceramide buildup.

Phase 1 and 2 Trials Show Promise

In the ongoing phase 2 clinical trial FAB-201, eight Fabry disease patients were treated with AVR-RD-01. AVR-RD-01 is a kind of stem cell treatment that modifies autologous hematopoietic stem cells to create functional alpha-galactosidase A molecules before reintroducing them to the patient.

A modified virus (likely similar to the Adeno-Associated Virus commonly used in similar gene therapy treatments) delivers a functionl GLA gene to the harvested stem cells. Once these modified cells are re-injected into the host, scientists hope the now-functional enzymes will proliferate throughout the body.

AVR-RD-01 has produced impressive results in select patients — in a trial patient who had not formerly received enzyme replacement therapy, a 12-month follow up found an 87% reduction in the presence of toxic globotriaosylceramide metabolites.

The first four participants all experienced significant reductions in lysosomal globotriaosylceramide levels, even when compared to enzyme replacement therapies. All experienced a reduction between 33 and 41 per cent.

Broadly, AVR-RD-01 seemed to bring lasting clinical benefit to the limited number of patients who enrolled in these studies. Durable effects (enhanced alpha-galactosidase A activity) were sustained for over half a year.

Dr. Mark Thomas, principal investigator of AVR-RD-01’s phase 2 clinical trial, noted that the sustained healthy levels of globotriaosylceramide and its metabolites “could translate into substantially improved patient outcomes over the current standard of care.” However, further clinical trials will likely be conducted to confirm that the results are replicable.


Do you or does anyone you know live with Fabry disease? What are your thoughts on this exciting development? Patient Worthy wants to hear from you!

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