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Mhoriam Ahmed
Mhoriam Ahmed, fourth year PhD student, MRC Centre for Neuromuscular Diseases
I came to the Centre for Neuromuscular Diseases at the Institute of Neurology after completing a BSc in Biochemistry at University College London. The Centre particularly interested me as it is the first of its kind to bring together world renowned experts in neuromuscular diseases. It is therefore a fantastic opportunity to work with and learn from high calibre scientists. This program is even more attractive since it is a 4-year course in which the PhD students have the opportunity to undertake 3 three month projects in different laboratories during the first year, thus giving us a chance to gain experience in a wide range of approaches.
PhD Project:
Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy affecting predominantly males, over the age of 40. It has a prevalence of between 5-13 per million in Europe, Australia and North America (Mastaglia 2009).
sIBM is a debilitating condition which remains untreatable. The disease has a highly selective pattern of muscle involvement, typically affecting muscles such as the quadriceps femoris and forearm flexors.
Although sIBM has long been considered an immune-mediated disorder, immune-based therapies have not proven beneficial. However, in addition to inflammatory features, sIBM muscle also displays degenerative features which distinguish it from the established primary inflammatory myopathies. Thus, in addition to myofibre infiltration by cytotoxic T-cells, in sIBM there are intracellular protein aggregates, vacuolation and proteasomal dysfunction which suggests that a more complex pathological process than inflammation alone, is involved in the disease pathogenesis. It is therefore likely that a broader therapeutic approach may be necessary for the treatment of sIBM.
Our aim is to use primary muscle cultures to model the inflammatory and degenerative aspects of sIBM in order to investigate the underlying pathophysiology of the disease. At present we are investigating the effects of cytoplasmic accumulation of proteins on cellular functions and the cytoprotective heat shock protein response. In addition, we are examining the effects of inflammatory mediators and proteasome inhibitors on cell viability.
In order to undertake these experiments we have to first establish and optimize a reliable and reproducible in-vitro model of sIBM using muscle cultures of high purity with minimal contamination from fibroblasts, adipocytes and other non-myogenic cells. This is particularly important when undertaking biochemical analysis of primary cell cultures.
Although the cause of sIBM is yet to be established, we hope that investigating the downstream pathological effects may identify therapeutic targets for drug development for this debilitating disease.
