This study is of one two studies published in the journal that focus on spinal muscular atrophy (SMA) type 1. The second study (open-label, phase 1–2; n= 15) investigated the use of gene therapy, which involved a single intravenous administration of nonreplicating adenovirus (scAAV9 [self-complementary adeno-associated viral serotype 9]) vector that included the normal human SMN1 sequence. Treatment was reported to result in longer survival, superior achievement of motor milestones, and better motor function than in historical cohorts.
An editorial notes that the therapeutic approaches in these two studies have a common objective, to increase the production of SMN protein in motor neurons and thereby improve motor function and survival. Because of the different study designs, it is hard to compare the results of these two studies. It notes that an important advantage of scAAV9 gene therapy is that it may require only a single intravenous infusion, whereas nusinersen probably requires lifelong repetitive intrathecal treatment. It adds that follow-up has been short in both studies, and the durability of the effects is uncertain for both treatments. It postulates that if the expression of the scAAV9 gene therapy declines over time, the same treatment may not be able to be repeated, because antibodies against AAV capsid proteins are anticipated to form. Furthermore, as the children grow, the phenotype may expand to affect other organs and tissues, which would then require confirmation that therapies such as scAAV9 and antisense oligonucleotides target other cell types. It stresses that neither therapy currently provides a cure and wonders if there is any benefit from starting treatment earlier (NURTURE study is currently investigating nusinersen in presymptomatic patients) or combining the two treatments. It acknowledges that an important constraint is the high anticipated cost of $750,000 for a course of nusinersen during the first year of therapy.
The scAAV9 gene therapy has not yet been approved, whereas nusinersen is approved for use in children and adults with SMA in US and EU. Nusinersen for treating SMA is on the NICE work programme at the scoping stage.
In its urgent clinical commission policy, NHS England has concluded that there is sufficient evidence to support a proposal for the routine commissioning of nusinersen for SMA Type 1 under certain criteria. This policy statement will be formally reviewed after the outcome of the NICE appraisal or termination of the Expanded Access Programme scheme.