Understanding the mechanisms by which a genetic variation contributes to diseases is a central aim of human genetics and should greatly facilitate the development of preventive strategies and treatments. Implementing this approach to understand the cellular and molecular basis of neuromuscular disorders (NMDs) is particularly challenging due to the inherent inaccessibility of the affected cell types from patients. Despite the wealth of existing cellular and animal models, progresses towards identification of new treatments have been hampered by the incomplete understanding of the pathogenic mechanisms involved in these diseases as well as the availability of relevant screening tools. The development of convenient Human models that even more closely replicate the disease will undoubtedly improve pathological modeling of neuromuscular disorders as well as more adapted therapeutics.

In this context, my group is interesting in developing an in vitro human “tool box” to establish pathological models of representative NMDs based on the use of human pluripotent stem cells. While developing these models, our proposal has several objectives: (1) deciphering the pathophysiological mechanisms of different NMDs (2) to use biomarkers revealed by the mechanistic approach as readouts for drug screening and (3) validate these developments by a proof-of-concept high-throughput screening (4) to convert these models into therapeutic products.

[Invitation by Latif Rachdi]