Autophagy and Lysosomes in Pompe Disease

Citations Over TimeTop 10% of 2006 papers

Abstract

In Pompe disease, a deficiency of lysosomal acid alpha-glucosidase, intralysosomal glycogen accumulates in multiple tissues, with skeletal and cardiac muscle most severely affected.(1) Complete enzyme deficiency results in rapidly progressive infantile cardiomyopathy and skeletal muscle myopathy that is fatal within the first two years of life. Patients with partial enzyme deficiency suffer from skeletal muscle myopathy and experience shortened lifespan due to respiratory failure. The major advance has been the development of enzyme replacement therapy, which recently became available for Pompe patients. However, the effective clearance of skeletal muscle glycogen, as shown by both clinical and preclinical studies, has proven more difficult than anticipated.(2-4) Our recent work published in Annals of Neurology(5) was designed to cast light on the problem, and was an attempt to look beyond the lysosomes by analyzing the downstream events affected by the accumulation of undigested substrate in lysosomes. We have found that the cellular pathology in Pompe disease spreads to affect both endocytic (the route of the therapeutic enzyme) and autophagic (the route of glycogen) pathways, leading to excessive autophagic buildup in therapy-resistant skeletal muscle fibers of the knockout mice.

Related Papers

• → Glycogenosis type II (acid maltase deficiency)(1995)163 cited
• → Glycogen storage disease type II: Genetic and biochemical analysis of novel mutations in infantile patients from Turkish ancestry(1998)24 cited
• → Glycogen storage disease type II: Genetic and biochemical analysis of novel mutations in infantile patients from Turkish ancestry(1998)2 cited
• → Experience with Adult Pompe Disease Treated at Home with Myozyme(2011)
• Enzyme replacement therapy for Pompe disease(2010)