Gene Therapy Makes Strides for Infants With Spinal Muscular Atrophy

Baby boy learning to walk with father hand in living room toddler boy
During the AAN 2021 Virtual Annual Meeting, investigators presented their findings on the safety and efficacy of onasemnogene abeparvovec (formerly AVXS-101) in presymptomatic SMA patients with 3 copies of the survival motor neuron 2 gene.

The following article is part of conference coverage from the American Academy of Neurology (AAN) 2021 Virtual Annual Meeting. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from the AAN 2021 Virtual Annual Meeting.

Treatment with gene therapy medication onasemnogene abeparvovec was associated with improvements in standing and independent walking ability in pediatric patients with presymptomatic spinal muscular atrophy (SMA) younger than 2 years of age, according to research presented at the American Academy of Neurology 2021 Virtual Annual meeting, held April 17 to 22, 2021.

Patients with SMA typically experience a loss of motor and respiratory function caused by SMN1 deletion or mutation. The presence of survival motor neuron 2 gene (SMN2) copies may modify the severity of the disease. Approximately 85% of patients with 3SMN2 develop symptoms during infancy. These symptoms include an inability to walk independently without assistance.

In the ongoing, open-label, phase 3 SPR1NT ( Identifier NCT03505099), study researchers evaluated a 1-time intravenous infusion of onasemnogene abeparvovec through 24 months in asymptomatic patients with 3 copies of SMN2 who were expected to develop SMA.

The primary outcome was the ability to stand unassisted for 3 or more seconds, while the secondary outcome was independent walking. The study researchers also evaluated the incidence of adverse events (AEs) and serious AEs (SAEs) associated with the therapy.

A total of 15 patients have been enrolled in cohort 2 of the study as of June 2020. The median age of the patients at the last study visit was 15.2 months, and the median follow-up was 14.5 months.

The primary efficacy endpoint of unassisted standing for 3 or more seconds within the normal development window was achieved in 8 patients (16.9 months). The other 7 patients who did not experience the primary efficacy endpoint were all younger than 16.9 months of age.

In addition, 6 patients were able to walk independently, an ability consistent with normal development (17.6 months). The remaining patients who did not meet this endpoint were all younger than 17.6 months.

All 30 patients included in the safety population (2SMN2 [n=14]; 3SMN2 [n=15]; 4SMN2 [n=1]) experienced at least 1 AE during the study. A total of 17 out of 30 patients experienced a treatment-related AE, while 7 out of 13 experienced a SAE. All SAEs, however, resolved and were considered unrelated to the study therapy.

The study researchers concluded that treatment with onasemnogene abeparvovec was associated with achievement in “gross motor milestones similar to [nonSMA], typically developing peers, demonstrating a significant therapeutic benefit.”


Strauss K, Muntoni F, Farrar M, et al. Onasemnogene abeparvovec gene therapy in presymptomatic spinal muscular atrophy (SMA): SPR1NT study update in children with 3 copies of SMN2. Presented at: the American Academy of Neurology 2021 Virtual Annual Meeting; April 17-22, 2021. Abstract S4.001