Of the many forms of spinal muscular atrophy (SMA), the form causing predominately proximal muscle deficit and associated with a lack of the SMN protein is by far the most common form in children. This condition is diagnosed by identifying a homozygous deletion in the SMN1 gene, found in 98% of cases. The prognosis can, in part, the deduced from the number of copies of a paralogous gene called SMN2. Several innovative therapies resulting from knowledge of these genes are now available, including one based on antisense oligonucleotides. Marketed as nusinersen, and injected by the intrathecal route, these antisense oligonucleotides allow the SMN protein to be re-expressed.
In an article published in May 2019, a consortium of American researchers reported the first results of the follow up of children and adolescents with type II (n=11) or type III (n=17) SMA treated with nusinersen in the context of one of the pivotal trials, then treated routinely at the standard dose (12 mg every four months). The clinical data for the 28 participants, including mainly functional parameters (modified Hammersmith scale, 6-minute walk test, upper limb deficiency scale, etc.), were analysed. This analysis showed, after almost 3 years of treatment with nusinersen, a notable clinical improvement, especially pronounced in type II patients. However, the electrophysiological parameters had hardly changed. Finally, the authors emphasised the fact that the product was well tolerated.
A new retrospective study evaluating the respiratory function of 12 children with type II or III SMA, 4 to 12 years of age and taking nusinersen, was published in March 2021 by a German team. It did not report any significant change in respiratory function between the beginning of treatment (baseline) and 300 days later. The authors suggested that since the children had been treated relatively late, these results should be confirmed over a longer period of time and on a larger scale.
