Role of the neuromuscular junction as a therapeutic target in SMA

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by progressive degeneration of lower motor neurons in the spinal cord, resulting in skeletal muscle atrophy and muscle weakness. Increasing evidence suggests that impaired neuromuscular junction (NMJ) can also be present in SMA. The authors of the present study recently reported the association between clinical and neurophysiological signs of neuromuscular junction dysfunction. Subsequently, it was proposed that the NMJ could be targeted for possible therapeutic intervention. A few studies have reported that ß2-adrenoceptor agonists, like albuterol, act on the neuromuscular junction, reducing weakness in myasthenia gravis mouse model and in congenital myasthenic syndrome. As albuterol has been used in clinical trials in SMA and is often also used in clinical practice, the question has arisen whether the clinical effects observed in SMA following the introduction of albuterol may be at least partly related to an improvement in neuromuscular junction activity. Here, the authors describe two type 3 SMA patients who were prospectively investigated with clinical and neurophysiological assessments following the introduction of albuterol.

Pera MC, Luigetti M, Sivo S, et al. Does albuterol have an effect on neuromuscular junction dysfunction in spinal muscular atrophy? Neuromuscul Disord. 2018 Oct;28(10):863-864.