ALS

ALS is a fatal neurodegenerative disorder of unknown etiology for which there is no effective treatment. Progressive denervation of neuromuscular synapses in the peripheral nervous system (PNS) and degeneration of upper and lower motor neurons in the central nervous system (CNS) result in muscle weakness, atrophy, paralysis and ultimately death within 2-3 years from the onset of symptoms. Initial presentation of ALS varies between affected individuals, and typically presents as spinal-onset disease (muscle weakness of the limbs), or bulbar-onset disease (difficulty with speech and swallowing). Sporadic ALS (sALS) accounts for 90% of cases and has no clear aetiology, while familial ALS (fALS) accounts for 10% of cases and contains an underlying genetic component. However, while these two forms differ in causation, they appear pathologically and clinically indistinguishable. There is no known cure for ALS. There are two approved medications to treat ALS, riluzole (a glutamate blocker) and edaravone (a free radical scavenger), but with limited efficacy. Riluzole, approved in 1995, is administered orally twice daily and delays time to tracheostomy or death in patients with ALS (Riluzole package insert 2016), prolonging survival by 2-3 months (Miller et al. 2012). Edaravone, approved in the US in 2017, is administered in courses intravenously and shows efficacy in only a small subset of patients with ALS.