Therapeutic options in SMA: latest developments

Spinal muscular atrophy (SMA) is the most common inherited neuromusculardisease in infancy, notably in the Middle-East where its prevalence isparticularly high. SMA is caused in 98% of cases by a homozygous deletionwithin the SMN1 gene located on chromosome 5q. This deletion results in adramatic decrease of SMN, a ubiquitous protein physiologically necessary forlower motor neuron survival. Close to the SNM1 gene lies an almost identicalgene called SMN2 whose copy number varies from one individual to another.While SMN1 encodes a full–length SMN protein, SMN2 encodes only a smallamount of it together with a non-functional form of SMN. Several therapeuticavenues are currently being explored in SMA based on different strategies.Either by overstimulating the production of full-length SMN by the remainingSMN2 genes or by modifying the way alternative splicing occurs where SMN2is expressed.Nusinersen, an anti-sense oligonucleotide injected intrathecally, showedpromising results in type 1 and type 2, and was recently approved by bothFDA and EMA after successful clinical trials. To date, 150 children with SMAhave been exposed in France to this novel, well tolerated, but very expensivemedication manufactured by Biogen Inc.In parallel, ongoing open-label clinical trials have shown similarly excitingresults with a gene therapy product developed by Avexis Inc. and injectedsystemically in type 1 SMA oligosymptomatic infants.A growing number of drugs/compounds are now in the pipeline for SMAincluding Olesoxime a motor neuron protector.However these new developments pose a number of ethical issues concerningnot only efficacy and outcome (survival of extremely disabled kids) but alsouneven access to treatment.