Sporadic inclusion body myositis: Possible pathogenesis inferred from biomarkers

Research output: Contribution to journalReview articlepeer-review

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Abstract

Purpose of review: The relevance of proteins that accumulate and aggregate in the muscle fibers of patients with sporadic inclusion body myositis (sIBM) is unknown. Many of these proteins also aggregate in other disorders, including Alzheimer;s disease, leading to speculation that sIBM pathogenesis has similarities to neurodegenerative disorders. Our review will discuss current studies on these protein biomarkers and their utility in sIBM diagnosis. Recent findings: Two 'classical' components of sIBM aggregates (amyloid β and phospho-tau) have been re-evaluated. Three additional components of aggregates (TDP-43, p62, and LC3) have been identified. The sensitivity and specificity of these biomarkers has been explored. Two studies suggest that TDP-43 may have clinical utility in distinguishing sIBM from other inflammatory myopathies. Summary: The fact that sIBM muscle accumulates multiple protein aggregates with no single protein appearing in every sIBM patient biopsy suggests that it is not presently possible to place pathogenic blame on any single protein (i.e. amyloid β or TDP-43). Instead changes in protein homeostasis may lead to the accumulation of different proteins that have a propensity to aggregate in skeletal muscle. Therapies aimed at improving protein homeostasis, instead of targeting a specific protein that may or may not accumulate in all sIBM patients, could be useful future strategies for this devastating and enigmatic disorder.

Original languageEnglish
Pages (from-to)482-488
Number of pages7
JournalCurrent opinion in neurology
Volume23
Issue number5
DOIs
StatePublished - Oct 2010

Keywords

  • TAR DNA binding protein-43
  • biomarkers
  • inclusion body myositis
  • inflammatory myopathies
  • proteostasis

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