Pros and cons of different ways to address dysfunctional autophagy in Pompe disease

Ann Transl Med. 2019 Jul;7(13):279. doi: 10.21037/atm.2019.03.51.

Abstract

Autophagy is a major intracellular self-digestion process that brings cytoplasmic materials to the lysosome for degradation. Defective autophagy has been linked to a broad range of human disorders, including cancer, diabetes, neurodegeneration, autoimmunity, cardiovascular diseases, and myopathies. In Pompe disease, a severe neuromuscular disorder, disturbances in autophagic process manifest themselves as progressive accumulation of undegraded cellular debris in the diseased muscle cells. A growing body of evidence has connected this defect to the decline in muscle function and muscle resistance to the currently available treatment-enzyme replacement therapy (ERT). Both induction and inhibition of autophagy have been tested in pre-clinical studies in a mouse model of the disease. Here, we discuss strengths and weaknesses of different approaches to address autophagic dysfunction in the context of Pompe disease.

Keywords: Lysosome; autophagy; enzyme replacement therapy (ERT); muscle.

Publication types

  • Review