Sporadic inclusion body myositis: new insights and potential therapy

Abstract

Purpose of the review: To describe new insights and developments in the pathogenesis, diagnosis and treatment of sporadic inclusion body myositis (IBM).

Recent findings: Various hypothesis about the pathogenesis of IBM continue to be investigated, including autoimmune factors, mitochondrial dysfunction, protein dyshomeostasis, altered nucleic acid metabolism, myonuclear degeneration and the role of the myostatin pathway. Serum autoantibodies against cytosolic 5'-nucleotidase 1A have been identified in IBM showing moderate diagnostic performance. The differential diagnostic value of histopathological features, including different protein aggregates, continues to be evaluated. MRI may also be of monitoring value in IBM. New therapeutic strategies are being tested in IBM patients, namely the upregulation of the heat shock response and the antagonism of myostatin.

Summary: Recent important advances have occurred in IBM. These advances, including recent and ongoing clinical trials, may lead to earlier diagnosis and improved understanding and treatment of the disease. Despite improved knowledge, IBM continues to be a puzzling disease and the pathogenesis remains to be clarified. An interdisciplinary, bench to bedside translational research approach is crucial for the successful identification of novel treatments for this debilitating, currently untreatable disorder.

Figure 1

Potential pathogenic mechanisms leading to myofibre injury in sporadic inclusion body myositis

Figure 2. Characteristic p62 staining pattern in inclusion body myositis (as suggested by Brady et al [39])

The following pattern of p62 immunoreactivity is more characteristic of IBM: strongly stained, discreet and clearly delineated, round or angular aggregates, variable in number and size within a muscle fibre but rarely filling it and predominantly located subsarcolemmal, but also perinuclear and adjacent to vacuoles.

Figure 3. Muscle MRI of a patient suffering from sporadic inclusion body myositis (IBM) and from a healthy control

Axial MRI images of a patient with IBM (A–D) and a healthy control (E–H) with MRI T1-weighted images on the left and the short tau inversion recovery (STIR) images on the right side. Increased signal within muscles on T1-weighted sequences indicate fatty infiltration whilst on STIR sequences indicate muscle oedema. The patient shows abnormalities typical of IBM with fatty atrophy of the quadriceps muscles in the thigh (A, arrows) and most marked involvement of medical gastrocnemius in the calf (C, arrowhead). Muscle inflammation is evident within many thigh muscles (B) and within gastrocnemius in the calf (D). Corresponding images for a healthy volunteer show homogenous low signal intensity within muscles.