Endocrine / Metabolic

Mouse studies suggest gene therapies delivering secretion-optimized GAA variants could help treat Pompe’s disease. The gene therapies consist of a liver-tropic adeno-associated viral serotype 8 (AAV8) vector encoding one of two GAA variants in which the N-terminus was deleted for enhanced secretion and the secretory signal peptide was replaced with a signal peptide from AAT or CTBR2. In a mouse model of Pompe’s disease, each gene therapy decreased cardiac hypertrophy and glycogen levels in the brain, heart and skeletal muscle and increased motor neuron numbers in the spinal cord, skeletal muscle strength, respiratory function and survival compared with vehicle. Next steps include additional testing of the safety and efficacy of the gene therapies in animal models of Pompe’s disease.

Amicus Therapeutics Inc. has ATB200, an enzyme replacement therapy (ERT) consisting of recombinant human GAA (rhGAA), in Phase I/II testing to treat Pompe’s disease. Amicus also has ATB200/AT2221, a co-administered therapy comprising ATB200 and the pharmacological chaperone AT2221, in Phase I/II testing to treat Pompe’s disease...