NEMMYOP

Nemaline myopathy (NM) is a rare neuromuscular disorder characterised by muscle weakness and the presence of strucural anomalies (called “rods”) in the muscle fibres. Most of the studies and research projects conducted over the last two decades, mainly aimed at identifying the genes responsible for NM but the corresponding functional aspects have not been investigated.. Additionally, given that the mechanisms underlying muscle weakness in NM are poorly understood, therapeutic strategies have been often symptomatic and empirical and no treatment was available. The general objective of this project was to assess skeletal muscle function in both patients and mouse models of NM in order to better understand the causative mechanisms of the force reduction occurring in NM. For that purpose, we combined measurements of force production at various levels (i.e., ranging from molecular to the whole muscle) with biochemical and non-invasive nuclear magnetic resonance (NMR) investigations.

We demonstrated that the altered muscle function in both animals and NM patients was related to defects in a specific part of the muscle called “sarcomeric proteins”. On the basis of NMR investigations, we identified several markers that could be used for monitoring the severity and/or the progression of NM and for assessing the efficacy of potential therapeutic interventions. Interestingly, we originally demonstrated that a class of pharmacological agent (called “troponin activators”) might be a relevant therapeutic strategy to improve force in NM patients and in other neuromuscular disorders.