Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial

Nat Med. 2022 Jul;28(7):1390-1397. doi: 10.1038/s41591-022-01867-3. Epub 2022 Jun 17.


Most children with biallelic SMN1 deletions and three SMN2 copies develop spinal muscular atrophy (SMA) type 2. SPR1NT ( NCT03505099 ), a Phase III, multicenter, single-arm trial, investigated the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated within six postnatal weeks. Of 15 children with three SMN2 copies treated before symptom onset, all stood independently before 24 months (P < 0.0001; 14 within normal developmental window), and 14 walked independently (P < 0.0001; 11 within normal developmental window). All survived without permanent ventilation at 14 months; ten (67%) maintained body weight (≥3rd WHO percentile) without feeding support through 24 months; and none required nutritional or respiratory support. No serious adverse events were considered treatment-related by the investigator. Onasemnogene abeparvovec was effective and well-tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Humans
  • Infant
  • Muscular Atrophy, Spinal* / genetics
  • Spinal Muscular Atrophies of Childhood* / genetics
  • Spinal Muscular Atrophies of Childhood* / therapy
  • Survival of Motor Neuron 2 Protein / genetics


  • SMN2 protein, human
  • Survival of Motor Neuron 2 Protein

Associated data

  • ClinicalTrials.gov/NCT03505099