Gene Therapy for Fabry Disease

Mutations in the GLA gene are known to cause Fabry disease, resulting in the body producing less of an enzyme called alpha-galactosidase A. This enzyme is responsible for breaking down a fatty substance called globotriaosylceramide (Gb3 or GL-3). Due to the mutations, this enzyme does not work properly and Gb3 accumulates inside cells. The subsequent damage affects organs and systems such as the kidneys, heart, skin, brain, nerves, and intestinal tract.

Gene therapy for Fabry disease is designed to introduce a healthy copy of the GLA gene inside cells to restore normal levels of the alpha-galactosidase A enzyme. This approach is still in the experimental stages.

How does gene therapy work?

Every cell in the body contains genes that carry instructions to make specific proteins. Gene therapy works by inserting new, properly functioning copies of genes inside cells, so that the cellular machinery can produce the right proteins in necessary amounts. 

To introduce new genes into the cell, a vector or a “gene carrier” is necessary. This is usually a virus, called a viral vector, that scientists have modified so it is no longer harmful. 

Gene therapy is a technique that researchers are investigating as a treatment for many diseases, including cancer and neurodegenerative disorders.

Gene therapy for Fabry disease

Researchers have successfully used gene therapy in animal models of Fabry disease to raise the levels of the alpha-galactosidase A enzyme and clear Gb3 buildup from organs. There are many gene therapy candidates in development.


Researchers have already tested AVR-RD-01, by Avrobio, in people. In 2017, a Canadian man became the first person with Fabry disease to receive the gene therapy compound. Researchers collected his blood stem cells, modified them with a lentiviral vector, a type of viral vector, which was carrying a healthy copy of the GLA gene, and returned them into his body. The patient’s alpha-galactosidase A levels rose to normal levels at 45 days after treatment, and a six-month checkup found consistency in normal levels, with no serious side effect. The man was tolerating AVR-RD-01 well.

AVR-RD-01 continues to be investigated in an open-label Phase 1 clinical trial, called FACTS (NCT02800070), in Canada and a Phase 1/2 clinical trial, called FAB-GT ((NCT03454893), with sites in the U.S., Canada, and Australia. Preliminary results of the trials suggest that AVR-RD-01 increases the levels of alpha-galactosidase A and decreases the levels of GB3 in patients, even after multiple years. The FAB-GT trial continues to recruit patients age 16 to 50.


FLT190 is an experimental gene therapy that Freeline is developing. A Phase 1/2 clinical trial (NCT04040049) is currently recruiting up to 15 patients, ages 18 and older, at sites in Italy, Norway, and the U.K. This study will assess the safety and efficacy of the treatment. Researchers expect to finish in December 2021. Enrollment and contact information is available here.


ST-920 is an experimental gene therapy for Fabry disease that Sangamo Therapeutics is developing. The therapy has shown promising results in a mouse model of this disease.

A Phase 1/2 clinical trial (NCT04046224) is currently recruiting about 30 adults with Fabry disease in the U.S. to test the safety and efficacy of ascending doses of a single infusion of this therapy. About six sites across the U.S. are enrolling eligible patients; contact and other information is available here. This trial in due to conclude in November 2021.

Other details

Gene therapy is a relatively new treatment approach. Therefore, scientists cannot say with certainty what common or serious side effects might accompany its use, or if any given gene therapy will be one-time treatment that might last a lifetime. 


Last updated: Dec. 27, 2020


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