Current treatments of spinal muscular atrophy in adults

Abstract

Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disorder related to motor neuron degeneration. SMA patients present generally severe muscular weakness and atrophy, which can reduce life expectancy and lead to severe functional disability. In recent years, the management of this condition has been revolutionized by the development of innovative therapies that target alternative splicing of pre-messenger SMN2 RNA by antisense oligonucleotides or small molecules and by the approval of the first vector-based SMN1 gene therapy. The high significance of the trials in children led to fast-tracking of these therapies to all SMA patients despite the absence of data in adults. Real-life data are progressively providing a better understanding of the expected benefits and tolerability. They also highlight the difficulties of evaluating these patients and the need to take into account the patients’ reported expectations and outcome. A review of the main data in adult patients is presented. The mechanisms of action of these innovative therapies are discussed as well as the limits of evaluations of these therapies in adults with longstanding severe amyotrophy.