FDA Approval of Nusinersen for Spinal Muscular Atrophy Makes 2016 the Year of Splice Modulating Oligonucleotides

With the Food and Drug Administration (FDA) approval of nusinersen (tradename Spinraza) for treatment of spinal muscular atrophy patients on December 23 [1], 2016 brought us not one, but two approved splice modulating oligonucleotides to treat neuromuscular disorders.Eteplirsen, an oligonucleotide to treat a subset of Duchenne muscular dystrophy (DMD) patients, was approved earlier this year.However, where the approval of eteplirsen was highly controversial [2], this one seemed to be crystal clear: the drug was approved only 91 days after Bioeen filed the new drug application (NDA) with FDA, and the application was not referred to an FDA advisory committee because "outside expertise was not necessary and there were no controversial issues that would have benefited from advisory committee discussion" [3].Spinal muscular atrophy is an autosomal recessively inherited disease, that is characterized by progressive loss of motorneurons, leading to muscle atrophy and paralysation.Most patients (60%) suffer from the most severe form of the disease, type I SMA.Symptoms start in infants before 6 months of age, patients never achieve independent sitting, need intensive supportive care, including ventilation, and seldom live beyond two years of age.Type II and type III SMA are milder forms of the disease.For type II onset is after 6-18 months, patients are able to sit independently but never able to walk and can live 20-40 years with good supportive care.Type III SMA patients are able to walk, but generally loose this ability when disease progresses.Survival is normal.It should be noted that all types of SMA are severe and debilitating and that the term "milder" is only relative to the very severe type I SMA.There is a type IV SMA, with onset in adulthood (after 30 years of age) and a slowly progressive course, but this is a very rare form [4].