NEMMYOP

The aims of the present proposal are i) to determine the mechanisms underlying muscle weakness and fatigability in the unique murine model with nebulin mutation and ii) to characterize the effects of therapeutic strategies. For the first time in nemaline myopathy (NM), two therapeutic approaches including transgenic expression of nebulette and adenoviral expression of Z-disk nebulin will be evaluated. To achieve these goals, the work will be carried out as a collaborative project between three research groups, each with a long-standing and unique experience in his field. The corresponding network will combine complementary expertises ranging from non invasive magnetic resonance imaging and spectroscopy coupled to measurements of muscle force in living animals (group 1); invasive methods to dissect out the disease mechanisms at the whole myofibril level (group2), and/or cellular up to molecular levels (group 3). Our research project is clearly positioned at the level of a translational work from basic science to direct clinical application. It should go far beyond what is currently known and should have a significant impact on health and life quality of patients suffering from NM.