Nusinersen May Be Effective for Short-Term Motor Function Improvements in Spinal Muscular Atrophy
Nusinersen, an antisense oligonucleotide that increases functional survival motor neuron protein production from SMN2, was clinically effective for improving motor function.
Nusinersen, an antisense oligonucleotide that increases functional survival motor neuron (SMN) protein production from SMN2, was clinically effective for improving motor function in patients older than 7 months with spinal muscular atrophy type 1 (SMA1), according to a study published in Neurology.
Drug-naive patients with SMA1 aged 8.3 to 113.1 months old were treated with intrathecal injections of nusinersen between December 2016 and May 2017 (N=33). Investigators assessed efficacy and safety outcomes before and at 2 months and 6 months of treatment. Researchers collected data on survival, respiratory function, and nutritional status at each follow-up.
For the efficacy analysis, the researchers assessed motor function using the modified Hammersmith Infant Neurologic Examination Part 2 (HINE-2) and age-adjusted physiotherapist scales (eg, Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND] and the Motor Function Measure 20 or 32).
The investigators found no differences between patients with 2 and 3 copies of the SMN2 gene. After 6 months of treatment, survival was 100% and the modified HINE-2 score showed median 1.5-point progress compared with pretreatment (P <.001). On the CHOP INTEND scale, the median progress was 4 points in 17 patients by 6-month follow-up. A total of 9 patients were hospitalized during treatment, resulting in 17 hospitalizations in total. The majority of hospitalizations resulted from respiratory events, with 3 because of respiratory failure.
Limitations of the study included its small sample size and lack of a comparator or placebo group.
"It should be noted that many parents reported improvements during treatment with nusinersen that were not captured by the measures used and that were not predefined in data collection such as louder voice, better endurance, and more efficient coughing," the researchers added. "Better definition of these outcomes might be useful for long-term follow-up of these patients."
Aragon-Gawinska K, Seferian AM, Daron A, et al. Nusinersen in spinal muscular atrophy type 1 patients older than 7 months: A cohort study. Neurology. 2018;91:e1312-e1318.