Inclusion body myositis: Correcting impaired mitochondrial and lysosomal autophagy as a potential therapeutic strategy

Abstract

Inclusion body myositis (IBM) is a late onset sporadic myopathy with a characteristic clinical presentation, but as yet unknown aetiology or effective treatment. Typical clinical features are early predominant asymmetric weakness of finger flexor and knee extensor muscles. Muscle biopsy shows endomysial inflammatory infiltrate, mitochondrial changes, and protein aggregation. Proteostasis (protein turnover) appears to be impaired, linked to potentially dysregulated chaperone-mediated autophagy and mitophagy (a type of mitochondrial quality control). In this review, we bring together the most recent clinical and biological data describing IBM. We then address the question of diagnosing this pathology and the relevance of the current biological markers that characterize IBM. In these descriptions, we put a particular emphasis on data related to the deregulation of autophagic processes and to the mitochondrial-lysosomal crosstalk. Finally, after a short description of current treatments, an overview is provided pointing towards novel therapeutic targets and emerging regulatory molecules that are being explored for treating IBM. Special attention is paid to autophagy inhibitors that may offer innovative breakthrough therapies for patients with IBM.