Long-term benefits of nusinersen in later-onset spinal muscular atrophy

Abstract

Nature reviews | Neurology treatment with the antisense oligonucleotide nusinersen benefits patients with spinal muscular atrophy (sMa) type ii and type iii over 3 years, a new study shows. the results not only demonstrate the potential of nusinersen in older children, but also reveal that improvements continue over time in patients receiving this drug. sMa is a genetic neuromuscular disorder. the most common form is sMa type i, which has an age of onset <6 months, severely impairs motor development and leads to death. sMa types ii and iii have later ages of onset (7–18 months and >18 months, respectively), and patients can lose existing motor function over time. Previous trials have demonstrated that nusinersen slows or halts sMa progression in infantile-onset and later-onset sMa, but follow-up periods in these trials were limited. “we wanted to find out whether the drug could show benefit and safety in older children with later-onset sMa, up to the age of 15 years at enrolment,” explains Darras. “we also wanted to see whether this benefit could be observed for an extended period of time.” in the new study, the researchers analysed the motor function of 11 children with sMa type ii and 17 children with sMa type iii who received treatment with nusinersen, first as part of a phase ib/iia open-label trial and then as part of an extension study. the two studies provided a total follow-up period of ~3 years. Functional outcome measures included scores on the Hammersmith Functional Motor scale–expanded, the upper Limb Module and the 6-Minute walk test, and electrophysiological outcome measures included compound muscle action potential (CMaP) and quantitative multipoint incremental motor unit number estimation. Over the 3 years, mean scores in the motor function measures improved, and CaMP amplitude and area remained generally stable. “the results confirm prior findings but also provide evidence for longer-term efficacy and safety in an extended age range of patients,” says Darras. Furthermore, average motor function continued to improve throughout the 3 years of follow-up. “these results provide evidence for continued improvements over time, which is a novel finding,” states Darras. the researchers now intend to continue monitoring patients who are participating in a long-term safety study.