Prof. Laurent Schaeffer is the scientific and technical coordinator and Prof. Carole Vuillerot is the general coordinator of the clinical part of the RHU SMART, which was selected from among 92 applications and is one of the 17 winners of the fifth call for projects for university hospital research (Recherche Hospitalo Universitaire: RHU). This project is part of the third investment program for the future (PIA: Programme Investissements d'Avenir) (agreement ANR-21-RHUS-0007). The operator is the French National Research Agency (ANR: agence nationale de la recherche) which aims to support innovative and large-scale research projects in the field of health.
Proximal Spinal Muscular Atrophy (SMA), which includes infantile and juvenile spinal muscular atrophy, is a central concern in most neuromuscular disorders.
The revolutionary treatments developed by Roche, Novartis Gene Therapy and Biogen have created a new clinical entity: some children with severe forms of SMA will live to adulthood but will remain severely handicapped by persistent muscle atrophy.
There are no pharmacological treatments for this atrophy.

The team has given itself 5 years to achieve the following objectives:

- 1) Provide a natural history of treated SMA patients: clinical and biological description of SMA patients to adapt medical management and design future treatment protocols for treated SMA patients

- 2) Provide biomarkers of treated SMA patients with a particular focus on fatigue assessment. Fatigue is ubiquitous in neuromuscular diseases and in particular in SMA, however few biomarkers are available to accurately quantify this complex clinical manifestation that severely alters patients' quality of life.

- 3) To develop a pipeline of drug screens for muscle atrophy based on muscle cells from SMA patients.

- 4) Identify pharmaceutical compounds to address muscle atrophy in treated SMA patients (with splicing regulators or motor neuron specific gene therapy) as well as in SMA patients not eligible for currently marketed treatments.

This will allow to:

• Improve knowledge of the phenotype of treated patients to better prepare future therapeutic trials in this population
• Develop clinical outcomes adapted to this new population
• Develop biological biomarkers
• Develop therapeutic strategies targeting secondary muscle atrophy.