Primary muscle degeneration in sporadic Inclusion-Body Myositis: combining deep-proteome data in patient muscle tissue with novel cellular models to pinpoint key mechanisms driving inflammation and aberrant protein expression.

Sporadic Inclusion-Body Myositis (sIBM) is the most common myopathy in older adults and has a significant impact on the quality of life; no treatment exists to date. Histopathologically sIBM is characterized by degenerative as well as inflammatory features. In addition to this evident inflammation, striking similarities are observed between sIBM and neurodegenerative diseases. Alternative disease mechanism are suspected since sIBM has no classic genetic cause nor does it respond to immunosuppression as a "classic" inflammatory disorder would. Previously we have taken advantage of the availability of disease tissue due to diagnostic muscle biopsies. This allows 'proteomics' studies that capture the entire set of proteins in the diseased muscle and the key 'signatures' of the underlying mechanisms. A total of 61 muscle samples of sIBM-patients and controls were studied. Integrative data-analysis points towards three crucial disease pathways. These are involved in cell growth and repair, DNA damage response and inflammation-control. In the current project we will further study the role of these pathways by performing focused protein expression studies in muscle tissue and through the specific manipulation of these pathways in human-derived myoblast cell-lines in order to reproduce both sIBM pathology and proteomesignature. This novel cell system can be used as a disease model and will aid in the design of disease 'biomarkers' and therapies for sIBM.

Keywords:NEUROMUSCULAR DISEASES

Disciplines:Neurological and neuromuscular diseases