Sporadic inclusion body myositis

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 up-regulation 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.

Proteomics of rimmed vacuoles define new risk allele in inclusion body myositis

“…In contrast to other IIM, conventional immunosuppressants and immunomodulatory regimens have not been found to alter disease progression. 1,2 Typical myopathological features are inflammatory and degenerative changes, accompanied by rimmed vacuoles (RV) and protein aggregates. 2-6 The current manuscript intentionally focuses on these “degenerative features” in order to gain insight into one aspect of sIBM pathogenesis.…”

Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis

“…Sporadic inclusion body myositis (sIBM) is the most common myopathy among people aged >45 years, presenting a characteristic pattern of progressive muscle weakness and atrophy in both proximal and distal muscles, particularly in knee extensors and wrist and finger flexors (Machado et al., 2014). Muscle pathology in sIBM indicates a combination of inflammatory and degenerative features such as rimmed vacuoles, sarcoplasmic inclusions, and the deposition of degenerative proteins in affected muscle as pathologic hallmarks, which are features that differentiate sIBM from other muscle disorders (Machado et al., 2014).…”

“…Muscle pathology in sIBM indicates a combination of inflammatory and degenerative features such as rimmed vacuoles, sarcoplasmic inclusions, and the deposition of degenerative proteins in affected muscle as pathologic hallmarks, which are features that differentiate sIBM from other muscle disorders (Machado et al., 2014). Electromyography shows a myopathic and neurogenic pattern in some sIBM patients (Lotz et al., 1989), which resembles some hereditary inclusion body myopathies (hIBMs) and motor neuron diseases (Dabby et al., 2001, Lotz et al., 1989).…”

Myopathology of Adult and Paediatric Mitochondrial Diseases

“…These include infantile Pompe disease and adult-onset acid maltase deficiency [ 21 ], occasionally in muscular dystrophies such as LGMD2A [ 147 ] and FSHD [ 148 ] rarely primary lipid storage myopathies [ 126 ]. Muscle biopsies of patients with inclusion body myositis (IBM) may show increased numbers of RRF and COX-negative fibres [ 149 ]. In IBM, the on-going inflammation and cytokine environment, the associated production of reactive oxygen and nitrogen species, and the associated endoplasmic reticulum stress have a role in the initiation of mitochondrial DNA damage, leading to the accumulation of clonally-expanded mtDNA deletions and respiratory deficiency, a phenomenon that is not compensated by the malfunctioning cell repair mechanisms [ 150 ].…”