The search for treatments for inclusion body myositis

Inclusion body myositis is a rare, relentlessly progressive muscle disease affecting adults older than 45 years. It is associated with severe disability and consequently reduced quality of life. The pathogenesis is complex: the presence of inflammatory changes in skeletal muscle and presence of cytosolic 5′-nucleotidase 1A antibodies in serum suggest an autoimmune cause, but immunosuppressive or immunomodulating therapy has not proven to be beneficial. Pathological evidence also suggests a degenerative component, evident as protein aggregates in skeletal muscle. 1 Naddaf E Inclusion body myositis: Update on the diagnostic and therapeutic landscape. Front Neurol. 2022; 131020113 Crossref Scopus (2) Google Scholar The search for potential therapies has therefore moved away from solely aiming to influence the immune-mediated pathway. However, a trial of bimagrumab, which blocks the myostatin pathway, did not show beneficial effects. 2 Hanna MG Badrising UA Benveniste O et al. Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol. 2019; 18: 834-844 Summary Full Text Full Text PDF PubMed Scopus (83) Google Scholar In theory, a strategy of augmenting the heat shock response with arimoclomol might improve degradation of misfolded proteins and consequently reduce cell stress. Safety and efficacy of arimoclomol for inclusion body myositis: a multicentre, randomised, double-blind, placebo-controlled trialArimoclomol did not improve efficacy outcomes, relative to placebo, but had an acceptable safety profile in individuals with inclusion body myositis. This is one of the largest trials done in people with inclusion body myositis, providing data on disease progression that might be used for subsequent clinical trial design. Full-Text PDF Open Access