Pompe disease (or glycogen storage disease type 2) is due to a deficit in acid α-glucosidase enzyme (GAA) or acid maltase. The classic infantile form of Pompe disease occurs when neither of the two alleles produces a functional enzyme. The late onset forms of Pompe disease develop when GAA production is partially defective.
These GAA mutations cause glycogen accumulation in lysosomes, which causes cell damage in different tissues, particularly in the heart, muscles, liver and nervous system. Although all patients with Pompe disease suffer from GAA enzyme deficiency, the variability of the activity of the enzyme gives rise to a broad spectrum of disease profiles.
Pompe disease may be treated by Enzyme Replacement Therapy (ERT), but its efficacy is limited, it is associated with high immunogenicity, and it does not correct pathologic glycogen accumulation in nerve tissue and skeletal muscle.
Genethon has developed a gene therapy product which makes it possible to correct glycogen accumulation in the muscles and central nervous system, and to improve cardiac hypertrophy and muscular and respiratory dysfunction in a mouse model of the disease.
Genethon is collaborating with the biopharmaceutical company Spark Therapeutics to prepare a clinical trial.