Fatigability in spinal muscular atrophy : quantification, characterization and treatment

Abstract

Fatigability is frequently mentioned and considered as a highly debilitating impairment of daily life by many patients with SMA, but has nevertheless been given little priority for a long time. Until recently, clinical trials have been mainly focused on survival and early development of young infants with little understanding or sense of urgency with respect to fatigability despite this is an important problem for older patients. The results of these studies on fatigability in SMA will hopefully contribute to research and treatment of fatigability on three different levels. First, outcome measures are now available that can be used in clinical trials to assess efficacy in small heterogenous samples of children and adults with SMA. Secondly, we have demonstrated that fatigability is a highly prevalent additional dimension of physical impairment that requires attention and treatment. Third, we have demonstrated efficacy of a safe and low-cost treatment which can be used as an add-on therapy to genetic therapies or as an alternative for children and adults without access to expensive SMN-augmenting treatments. Fatigability in SMA is, however, a complex phenomenon of which the pathophysiological background, the impact on daily life and the optimal treatment will vary between patients. It is important to aim for a personalized approach in the near future, aiming to identify the main limiting factor, the most relevant outcome measures and the best treatment for each individual patient.