Treatment with nusinersen (Spinraza) produced significant improvements in motor function in children with spinal muscular atrophy type 1 even if treatment was initiated at a later age, new research has suggested.
In a paper published online Aug. 29 in Neurology, researchers presented the results of a prospective cohort study in 33 children who ranged in age from 8.3 months to 9.4 years and had spinal muscular atrophy type 1. In this study, the children were treated with the antisense oligonucleotide nusinersen, which increases production of functional survival motor neuron (SMN) protein. The patients participated in the trial as a part of an Expanded Access Program for nusinersen that’s operated by its manufacturer, Biogen.
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All previous trials of nusinersen have enrolled patients younger than 7 months, wrote Karolina Aragon-Gawinska, MD, of the Institute I-motion at Armand Trousseau Hospital, Paris, and her coauthors. The benefits of the drug in older patients were unknown.
The disease has a median survival of 8-13.5 months of age, yet all patients in the study were alive at 6 months after starting the treatment. Researchers saw a 1.5-point median improvement in motor milestones – measured using the Hammersmith Infant Neurologic Examination (HINE) Part 2 – and five patients were able to sit up without support for more than 30 seconds.
On the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scale, which assesses the motor skills of infants with spinal muscular atrophy, there was a median improvement of four points at 6 months.
There were no significant changes in the need for nutritional support. However, eight patients showed worsening respiratory condition at 6 months, compared with baseline. Three patients – all of whom had a more severe form of the disease by virtue of only having two copies of the nearly identical SMN2 gene – showed no significant motor progress and were placed on full-time ventilation.
Overall, the number of copies of SMN2 gene did not appear to affect the need for ventilator or nutritional support.
“The response to treatment was highly variable, but new motor acquisitions were attained even in 8-year-old patients,” the authors wrote. “In some patients, respiratory worsening was observed despite motor improvement, suggesting a slower action of nusinersen on the respiratory symptoms and the possible intercurrent infections that might destabilize these weak patients.”
They noted that while previous studies had included patients with only two copies of the SMN2 gene – and hence more severe disease – around half the patients in this study had three copies, which may explain why even older patients showed significant responses to treatment.
“Patients with three SMN2 copies were older and had a longer disease duration than patients with two SMN2 copies, which may partially explain the absence of copy number effect.”
The study was funded by the Institute of Myology and AFM-Telethon. Eight authors reported involvement with pharmaceutical-sponsored trials, consultancies, or other funding from the pharmaceutical industry, including Biogen. No other conflicts of interest were declared.
SOURCE: Aragon-Gawinska K et al. Neurology. 2018 Aug 29. doi: 10.1212/WNL.0000000000006281.