Rare diseases affect around 30 million people in Europe, of which 500,000 are affected with neuromuscular diseases (NMDs). NMDs, affecting both children and adults with a prevalence of 1 in a 1000 people, form a large and heterogeneous group of genetic diseases causing progressive degeneration of skeletal muscles. Most NMDs result in chronic long-term disability imposing a significant burden on patients, families, and public health care. In many cases, patients die prematurely from respiratory, and in some cases cardiac, muscle impairment. There are more than 200 NMDs, including over 30 types of Muscular Dystrophy (MD) which results from the mutation of genes controlling muscle functions and structures. Over 100 genes involved in MDs have already been identified; however, many are still to be discovered. The classification of MDs is not fixed but evolves with the constant discovery of new genes/mutations responsible for these diseases. In Europe, thousands of MDs patients currently have no molecular diagnosis. Late or inaccurate diagnoses delay the start of adequate treatments and may have irreversible consequences for the patients.
The goal of MUMDUPSC is to better understand the mechanisms contributing to previously undiagnosed MD (UMDs), to orient their diagnoses and facilitate their classification, in the hope that this may lead to new therapies. To reach this aim, MUMDUPSC met the three specific objectives:
1. Establishment of in vitro models recapitulating UMDs muscle phenotypes using patients hiPSC lines.
2. Identification of Genes whose expression is modulated in UMDs compared to control lines (unaffected and known MDs)
3. Identification of genetic alterations associated with UMDs in patients.
By combining disease modelling from patients’ hiPSC and state-of-the-art molecular and functional technologies, MUMPDUPSC objectives are to identify genes, biological pathways and functional properties affected in these various debilitating NMDs. Overall, through stem cells modeling, this project offers new avenues for understanding muscle pathologies and will, facilitate the development of innovative therapeutic approaches.
