Journal
AUTOPHAGY
Volume 2, Issue 4, Pages 318-320Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.2984
Keywords
glycogen storage disease type II; myopathy; acid alpha-glucosidase; enzyme replacement therapy; lysosomal disorder
Categories
Funding
- Intramural NIH HHS Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available