• Thesis 

Spinal muscular atrophy (SMA), a rare neuromuscular disease, is characterised by motor neuron degeneration due to the absence of the SMN1 gene and a deficiency in the SMN protein. Clinical manifestations vary widely: some patients with particularly severe forms (types 0 or 1) die before the age of 2 in the absence of treatment, while others maintain independent walking throughout their lives, with no reduction in life expectancy. Recently, three treatments restoring the SMN protein have been approved, improving the life expectancy and quality of life of patients with severe to mild forms of the disease.

However, despite these therapeutic advances, fatigability remains a major problem in SMA patients. The variability of clinical manifestations and the complexity of fatigue mechanisms make it difficult to gain a precise understanding of fatigability in this population.

Impaired neuromuscular function, resulting from motor neuron degeneration, contributes to fatigue, and muscle atrophy exacerbates weakness, limiting daily activities. The mechanisms of fatigue in SMA patients remain poorly explored, accentuating the need for specific tools to assess fatigability objectively.

In this context, we propose to transpose a quadriceps fatigability test (QIF test) that has already been validated in healthy populations. The aim of our project is to adapt it to the motor levels of different SMA patients in order to assess fatigability accurately, taking into account the different phenotypes. The aim is to determine the feasibility, reproducibility and relevance of this test with a view to gaining a better understanding of the aetiology of persistent fatigue in SMA patients. This study could provide the tools needed to assess fatigability objectively, both for regular clinical use and for future clinical trials, underlining the ongoing need for innovative solutions to the persistent challenges associated with fatigability in SMA.

Research Projet:  FANTASI-SMART

Supervisor: MILLET Guillaume

Start: 01/2025

End expected: