Update on Inclusion Body Myositis

Duaa Jabari, V. V. Vedanarayanan, Richard J. Barohn, Mazen M. Dimachkie

While sporadic inclusion body myositis (sIBM) is the most common acquired muscle disease after age 50, the pathogenesis of this disease is still poorly understood. In this review, we discuss our current state of knowledge in sIBM and provide an update on our current understanding of its pathophysiology and management. Lines of evidence in support of an inflammatory pathogenesis include inflammatory infiltrates in the target organ, NFκB activation, cytokine response, MHC I upregulation, and cN1A antibody. Refractoriness to immunotherapies has led to suggestion of a degenerative pathophysiology. Evidence for impaired protein homeostasis with misfolding burden is coupled with findings of endoplasmic reticulum stress, proteasome dysfunction, and mitochondrial lesion. Recent treatment trials have focused more on correcting the degenerative process or muscle growth rather than controlling the inflammation. There has been growing evidence toward degeneration as the primary process in sIBM. This is consistent with the refractory nature of this disease. Improving our understanding of this disease pathogenesis will propel efforts to find an effective therapy.