Advances in inclusion body myositis: genetics, pathogenesis and clinical aspects

ABSTRACT

Introduction: Inclusion body myositis is the most common acquired muscle disease affecting older adults. It has an insidious onset with a very specific pattern of muscle involvement, but the aetiopathogenesis is still unknown. Pathologically the combination of inflammatory changes, degenerative changes as well as mitochondrial and nuclear changes are seen, and probably all contribute to the loss of muscle, however the primary abnormality remains a mystery. Treatment is currently supportive, but clinical trials are ongoing and are directed at new targets.

Areas covered: Clinical profile, genetic susceptibility, pathogenesis and treatment

Expert opinion: Understanding the aetiopathogeneis is vital to identify future treatment targets. In addition, understanding the natural history and the roles of biomarkers including the anti-CN1a antibody is vital for designing future clinical trials in IBM, to be properly designed and of sufficient duration to detect clinically significant changes.

KEYWORDS:

• Clinical
• diagnosis
• genetics
• inclusion body myositis (IBM)
• pathogenesis
• sporadic inclusion body myositis (sIBM)

Article highlights

• Sporadic IBM is the most common acquired muscle disease of mid- and later life and is poorly responsive to conventional immune therapies

• Genetic susceptibility is likely to be polygenic, being most strongly associated with the HLA-DRB1 locus and 8.1 MHC ancestral haplotype, but mitochondrial and protein degradation genes may also be involved

• Multiple interacting molecular and structural abnormalities co-exist in sIBM muscle and contribute to muscle dysfunction and breakdown, but the primary abnormality is not yet known.

• Clearly elucidating the underlying pathogenetic pathways involved will be vital for identifying novel therapeutic targets

• Future clinical trial designs must take into account what is currently known about the natural history of the disease and variability in the rate of progression in order to be of sufficient power and duration to detect meaningful changes

This box summarizes key points contained in the article.

Acknowledgments

We acknowledge the valuable suggestions and contributions of Dr Jerome Coudert in his review of the manuscript and we acknowledge funding support from the Perron Institute for Neurological and Translational Research.

Declaration of interest

M Needham has received honoraria for educational talks for Novartis and Bristol-Myers-Squibb, for participation in advisory boards for Novartis and Bayer, and travel grants by Novartis and Biogen-Idec. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was funded by Institute for Immunology & Infectious Diseases, Murdoch University.