Nusinersen (Spinraza; Biogen, Cambridge, MA), a novel therapy approved by the Food and Drug Administration (FDA) for treatment of patients with spinal muscle atrophy (SMA). Results of an expanded access program study (NCT02865109) were published in Neurology. In this study, 33 children with Type 1 SMA who were ages 8 months to 9 years were given nusinersen intrathecally.
At evaluation 6 months after treatment, all patients have survived and are continuing treatment. Although the response to the drug was high variable among participants in the trial, all had significant muscle control improvements. Median progress on the modified Hammersmith Infant Neurologic Examination Part 2 (HINE-2) score was 1.5 points after 6 months of treatment (P < .001). Of the study’s participants who were 18 to 48 months when treatment was given, 5 were able to sit unsupported for the first time.
Children had no changes in feeding tube status if a feeding tube was already in use. Some children had worsening respiratory problems, suggesting that nusinersen is slower to act on respiratory symptoms and related infections that might destabilize weak patients. The need for respiratory support significantly increased over time for all patients.
These results suggest that children over age 7 months will benefit from treatment with nusinersen while also confirming benefits of early diagnosis and treatment, before feeding tubes and respiratory support are needed. Newborn screening for SMA is recommended.
Nusinersen is an antisense oligonucleotide treatment that increases levels of motor neuron protein (SMN) 2, by binding to a splice site on the mRNA encoding for the protein. Blocking that splice site results in increased production of full-length SMN2, which can serve the function of SMN 1, which when mutated causes SMA. In this study, there was no statistically significant difference in response to treatment between children with 2 versus 3 copies of the SMN2 allele.
Lead author Laurent Servais, MD, PhD of Pitié-Salpêtrière Hospital in Paris, France and Citadelle Hospital in Liège, Belgium said, “SMA type 1 is a devastating disease, and it is encouraging to see that nusinersen may also help people who are at a later stage in the disease process. “More studies need to be done as it is likely that there are still unidentified genetic factors that contribute to the differences in participants’ responses to the treatment.”Next Story