Comparative mass spectrometric profiling of the dystrophin complexome in normal versus pathological muscles with differing degrees of fibre degeneration

Duchenne muscular dystrophy is the most commonly inherited neuromuscular disease of early childhood. The disorder affects almost exclusively boys due to the fact that the defective gene is located on the X-chromosome. The skeletal musculature, the respiratory system,the heart and the central nervous system are majorly affected in dystrophic patients. Current treatments, including pharmacological applications to counteract general muscle wasting, as well as assisted ventilation to ease progressive cardio-respiratory complications and surgical intervention to treat spinal abnormalities, do not specifically target the underlying pathological mechanisms. Therefore, alternative approaches such as gene therapy have been suggested for the treatment of muscular strophies. Several clinical trials are currently testing non-pharmacological approaches, such as 'exon-skipping' therapy. These novel genetic drugs promise to convert severe muscle wasting disorders into milder forms, thereby decisively improving the quality of life for patients suffering from muscular dystrophies. In order to be able to properly evaluate and monitor these new genetic treatments, reliable molecular indicators of disease and therapy status are needed. In relation to establishing new dystrophy-related marker molecules, the proposed research will attempt to identify novel diagnostic, prognostic and therapy-monitoring indicators, as well as elucidate molecular and cellular details of fibre wasting in various dystrophic skeletal muscles. We plan to use the high-throughput screening procedure named proteomics for the identification of novel candidate molecules. Proteomics is the large-scale biochemical analysis of the entire protein complement of a muscle cell. This new discipline of muscle biology separates proteins based on their physicochemical properties. The identity of altered muscle proteins is then determined by mass spectrometry. The long-term goal of our research is to establish a reliable biomarker signature for Duchenne muscular dystrophy.

Award Date
01 July 2016
Award Value
€50,000
Principal Investigator
Professor Kay Ohlendieck
Host Institution
Maynooth University
Scheme
MRCG-HRB Joint Funding Scheme