Hello everyone. There are many review articles on IBM. This is the latest (a couple of days ago) and a good one. Its very technical and Ill do my best to summarize it. One thing that I see is, in an area like IBM research, is that there are no big breakthroughs and so small discoveries become all the more important. Knowledge is cumulative. It also seems that the understanding of sIBM and the description of it is a bit of a evolving phenomena. Most previous articles use the age 50; this article says that IBM predominantly affects individuals over 45. This article estimates the prevalence at up to 139 per million in populations over 50. However they note that the prevalence is likely higher due to undiagnosed and misdiagnosed cases. On average, it takes five years to diagnose the disease. Although more is being learned about what IBM does, the root cause remains unknown. This article lists10 major mechanisms that cause damage to the muscle in sIBM. How these mechanisms are related and their root cause is unclear. The article emphasizes the wide differences seen in both the muscle examinations (biopsies) and the clinical presentations (the pattern of muscle weakness) in patients. Lately, the clinical features have been emphasized more than the biopsy results. This is reflected in a new definition of the criteria for sIBM put forward by the European Neuromuscular Center. The article notes that use of MRI in diagnosis and monitoring progress is becoming more common. In terms of treatment, the article mentions an indirect treatment through the use of myostatin inhibitors. By indirect I mean that these treatments are not directly focused on sIBM, rather, they are intended to increase overall muscle mass with the idea that if there is an increase in overall mass, there may be gains in function (however, this would not alter the sIBM disease process itself). The article describes Bimagrumab (BYM338), and the preliminary positive results it has achieved (it is a myostatin inhibitor). Another approach uses gene therapy (using follistatin) to inhibit myostatin. One more direct approach is to try to influence the protein changes seen in sIBM. Studies using a drug called Arimoclomol have been positive and justify further research. In conclusion, the article states that important progress has been made in understanding IBM and these advances may improve diagnosis or eventually lead to the discovery of treatments in the future. Basic causes and exactly how the different disease mechanisms interact needs to be discovered. The future is hopeful. 1). Environmental factors (e. g., viral infection), ageing and genetic susceptibility. 2). Autoimmune attack (MHC-1 [major histocompatibility complex class I] up-regulation, T-cells, B-cells, plasma cells, macrophages, cytokines, autoantibodies) 3). Accumulation of toxic proteins (B-amyloid, phosphorylated Tau, alphaB-Crystallin, ubiquitin, others) 4). Myonuclear degeneration (Rimmed vacuoles with nuclear and lysosomal proteins, redistribution of myonuclear TDP-43 [TAR DNA-binding protein 43], myonuclear protein aggregates) 5). Endoplasmic reticulum stress (Increased levels of proteins of the unfolded protein response) 6). Impairment of protein autophagy (Accumulation of autophagy associated proteins such as LC3 [microtubule-associated proteins 1A/1B light chain 3], p62 [ubiquitin-binding protein p62], LAMP2A [lysosome-associated membrane protein 2] and NBR1 [next to BRCA1 gene 1 protein]) [Protein dyshomeostasis] 7). Disruption of the ubiquitin proteasome system (UPS) (Heightened ubiquitination of proteins) [Protein dyshomeostasis] 8). Myostatin signalling (Accumulation of myostatin in muscle fibres, FOXO [forkhead box protein] /Atrogin-1 induction) 9). Mitochondrial dysfunction (Diminished respiratory chain function, abnormal proliferation and accumulation of mitochondria) 10). Alterations of nucleic acid metabolism (Misregulation of nucleic acid metabolism, sarcoplasmic redistribution of hnRNPs [heterogeneous nuclear ribonucleoproteins]) Machado, P. M., Dimachkie, M. M., & Barohn, R. J. (2014). Sporadic inclusion body myositis: new insights and potential therapy. Current Opinion in Neurology, 591–598. doi:10.1097/WCO.0000000000000129
Posted on: Tue, 02 Sep 2014 02:39:29 +0000
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