Fabry Disease

Fabry disease (FD) is a rare, inherited (genetic) disorder resulting from buildup of globotriaosylceramide (GL-3) in cells throughout the body. FD affects less than one in 50,000 individuals worldwide.

FD is an X-linked disorder resulting from mutations in the GLA gene carried on the X-chromosome so males and females can be affected differently.

1. Males have 1 X-chromosome so 1 mutated X-chromosome is sufficient for disease
2. Females have 2 X-chromosome; 1 mutated X-chromosome (heterozygous or carrier) can still lead to serious disease 

FD is also known as Anderson-Fabry disease or alpha-galactosidase A deficiency.

In males, FD manifests by extremity pain, skin lesions, opacity of the cornea and lens of the eye, and eventual end-stage renal disease, cerebrovascular disease. In females, it is thought that they have milder symptoms and later onset and may also have serious cardiac, cerebrovascular, or renal events.

FD is caused by deficient activity of the enzyme alfa-galactosidase A (α-Gal A) due to mutations in the GLA gene. α-Gal A deficiency results in the inability to breakdown glycosphingolipids (substances like oils, waxes, and fatty acids) in cell membranes.

Currently available treatments addressing α-Gal A deficiency include:

1. Enzyme replacement therapy (ERT) and the chaperone therapy, Galafold
2. Multiple products under development, including alternative ERTs, chaperones, and gene therapies (AAV and ex-vivo HSC)

M6PT is exploring potential gene therapy products and ERT options to treat individuals with FD.