Pompe disease is caused by mutations in the GAA gene. GAA is responsible for producing the acid alpha-glucosidase (GAA) enzyme that is involved in breaking down a large, complex sugar molecular called glycogen. In Pompe, not enough GAA is produced, and glycogen accumulates in cells — especially muscle cells — and disrupts normal muscle function.
Gene therapy would aim to provide the body with a working copy of the GAA gene that is dysfunctional in Pompe, thus allowing the body to produce its own alpha-glucosidase enzyme. In doing so, it is thought a gene therapy could reduce the toxic accumulation of glycogen in cells and improve muscle function in Pompe disease patients.
There are no gene therapies approved for Pompe disease in the U.S. Several investigational gene therapies are in various stages of preclinical and clinical development.
No gene therapies for Pompe disease have progressed past Phase 1/2 clinical testing. Three investigational therapies — AT845, ACT-101, and SPK-3006 — are now in Phase 1/2 development. Such Phase 1/2 trials are designed to mainly test a treatment’s safety, side effects, and dosing before advancing to trials that will evaluate the therapy’s efficacy.