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

Jeong-A Lim, Naresh Kumar Meena, Nina Raben


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.