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Summary: Muscle biomarkers have suggested that IBM pathophysiology is linked to myonuclear degeneration and disordered nucleic acid metabolism. A blood biomarker has high diagnostic performance for IBM, and through identification of its target links, IBM autoimmunity and degeneration together, supporting the view that IBM pathophysiology includes abnormal nucleic acid metabolism.
Summary: IBM remains an enigmatic and often misdiagnosed disease. The pathogenesis of the disease is still not fully understood. To date, pharmacological treatment trials have failed to show clear efficacy. Future research should continue to focus on improving understanding of the pathophysiological mechanisms of the disease and on the identification of reliable and sensitive outcome measures for clinical trials. IBM is a rare disease and international multicentre collaboration for trials is important to translate research advances into improved patient outcomes.
Conclusion: Several recent data have helped to shed light on the complex pathology of IBM: it has been demonstrated that there are unique immune-mediated mechanisms, which include - apart from the known cytotoxic T-cell attack - the generation of specific antibodies. Several mechanisms such as autophagic activity and production of NO have been demonstrated to interlink the immunocascades and the degenerative component of the disease. It is generally accepted that a range of aberrant molecules such as [beta]-amyloid are overexpressed and accumulate in muscle fibers from patients with IBM. In spite of recent evidence suggesting that the yearly disease progression is approximately 5%, the information is still insufficient to conclude on the exact rate of progression due to disease variability, differences in age of onset, misdiagnosis, poor scales to capture clinically meaningful changes and the variable time the patients seek medical advice. Different treatment studies have been performed and some more are currently underway. Whether the weight of evidence favors agents toward arresting the inflammatory or the degenerative mechanisms remains yet unclear.
Novartis receives FDA breakthrough therapy designation for BYM338 (bimagrumab) for sporadic inclusion body myositis (sIBM).
New book edited by Valerie Askanas and W. King Engel. Muscle Aging, Inclusion-Body Myositis and Myopathies.
. . . it has been widely believed that B-cell autoimmunity is unimportant in IBM. After microarray muscle profiling studies in 2002 identified a brisk B-cell immunoglobulin transcriptional response, an antigen driven B-cell response in IBM muscle was defined. . . . In the present study, we report the use of proteomic approaches to identify the protein cN1A as a candidate IBM autoantigen. Subsequent Western and dot blot assays confirmed that the presence of cN1A autoantibodies is a common and highly specific feature of IBM. A contemporaneous study has independently arrived at the same conclusion. The presence of greater than 1 approximately 43 kDa band in some patients, noted previously and again here, suggests that some patients have autoantibodies to other autoantigens or to modified versions of cN1A. Although the refractoriness of IBM to immune therapies has led to uncertainty about its status as an autoimmune disorder, the identification of the cN1A autoantigen and demonstration of multiple cN1A epitopes firmly establishes specific antigen-driven autoimmunity in IBM. . . . No autoantibody testing is currently available for IBM . . . data suggest that Anti-cN1A autoantibody blood testing will identify patients with IBM early on in their disease course. . . . An IBM blood test of comparable accuracy to muscle biopsy could be of substantial clinical value.Article Here
IBM is refractory to all treatments known to be effective in the idiopathic inflammatory myopathies including prednisone . On occasion, there may be a transient and mild improvement in response to corticosteroids (CS) early on in the course of the disease  or the initial response to CS may be more dramatic in some cases, but is unfortunately followed by progressive resistance to therapy over 3 to 6 years . Furthermore, in a long-term observational study of 136 patients, those who received immunosuppressive treatments (52%) were more severely affected on disability scales and on the sporadic inclusion body myositis weakness composite index when compared with those that did not . Progression toward walking handicap was more rapid among patients receiving immunosuppressive treatments. Because immunosuppressive treatments do not ameliorate the natural course of IBM, it has become more controversial whether to offer CS early on in the course of IBM . Despite an earlier encouraging report , randomized controlled trials of IVIG without CS [35, 36], and with CS  did not show significant benefit.
Conclusions IBM is the most common inflammatory myopathy after age 50 years. Despite similarities with PM, it is likely that IBM is primarily a degenerative disorder rather than autoimmune muscle disease. The clinical phenotype of IBM is distinctive, presenting with proximal leg and distal arm weakness. IBM is refractory to known treatments. Recent evidence suggests that chronic CS therapy may lead to worsening IBM disability on the long-term.Article Here
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