Researchers discovered that patients aged 24 months and younger with spinal muscular atrophy (SMA) and patients previously treated with nusinersen benefited significantly from gene therapy with onasemnogene abeparvovec, according to a study published in The Lancet Child & Adolescent Health. However, concerns about adverse side effects remain.

Nusinersen is the first gene-modifying drug approved for SMA, and it works by acting as a splicing modifier of the SMN2 gene. Another gene-modifying drug was developed later—called onasemnogene abeparvovec—which works by delivering the human SMN1 gene via an adeno-associated viral vector serotype 9 via a single intravenous dose. Onasemnogene abeparvovec has gained approval for use in the United States for patients aged less than 2 years, while in Europe it is approved for use in SMA type 1 patients of all ages as well as patients with 3 or fewer SMN2 copies.

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In view of the novelty of gene replacement therapy, researchers conducted a multicenter prospective observational study with the goal of accumulating real-world data on the efficacy and safety of onasemnogene abeparvovec. They recruited all children with SMA types 1 and 2 who were receiving onasemnogene abeparvovec treatment at 18 pediatric neuromuscular centers in Germany and Austria.

The research team assessed motor function upon the initiation of gene therapy and at 6 months afterward. Pediatric patients who were previously treated with nusinersen had their motor function assessed before and after the switch in treatment.

Seventy-six patients were analyzed in this study, with 58 of them previously receiving nusinersen. The researchers used the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) score to evaluate motor function. They discovered that CHOP INTEND scores increased significantly in children aged 24 months and below in the 6 months after the initiation of onasemnogene abeparvovec.

“In the 45 children pretreated with nusinersen and had available data, CHOP INTEND score increased by 8.8 points at 6 months after gene replacement therapy,” the researchers reported. They also observed serious adverse effects in 8 children, including acute liver dysfunction, pyrexia, vomiting, loss of appetite, and thrombocytopenia.

The research team wrote, “In conclusion, onasemnogene abeparvovec treatment in children with SMA up to 15.0 kg bodyweight is effective and safe, provided that patients are carefully selected and closely monitored regardless of previous nusinersen treatment.” This conclusion echoes the consensus guidelines recommended in Europe for onasemnogene abeparvovec.


Weiß C, Ziegler A, Becker LL, et al. Gene replacement therapy with onasemnogene abeparvovec in children with spinal muscular atrophy aged 24 months or younger and bodyweight up to 15 kg: an observational cohort study. Published online October 28, 2021. doi:10.1016/S2352-4642(21)00287-X