Proud C.M.Vũ D.C.Wilmshurst J.M.Sanmaneechai O.Gulati S.Xiong H.Moreno H.C.Tay S.K.H.Thong M.K.Born A.P.Banzzatto Ortega A.Jong Y.J.Al-Muhaizea M.A.Lee A.W.Visootsak J.Tauscher-Wisniewski S.Alecu I.Parlikar R.Finkel R.S.Jong Y.J.Ortega A.B.Thong M.K.Vũ D.C.Mahidol University2025-12-262025-12-262025-01-01Nature Medicine (2025)10788956https://repository.li.mahidol.ac.th/handle/123456789/113672STEER (NCT05089656) was a 52-week, phase 3, multicenter, randomized, sham-controlled, double-blind trial evaluating intrathecal onasemnogene abeparvovec (OAV101 IT), a one-time gene transfer therapy, in patients with spinal muscular atrophy (SMA). Participants ranged in age from 2 years to <18 years, were treatment-naive and were able to sit but never walked independently. Primary efficacy endpoint was change from baseline in Hammersmith Functional Motor Scale-Expanded (HFMSE) score. In total, 126 patients received OAV101 IT (n = 75) or a sham procedure (n = 51). The primary endpoint was met: patients treated with OAV101 IT demonstrated a significant increase in HFMSE score compared with sham (least squares mean difference, 1.88 (95% confidence interval: 0.51−3.25); P = 0.0074). Overall incidence of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI) was similar between groups. Transaminase increases were infrequent; most were low grade and transient. Two participants in the OAV101 IT arm and one participant in the sham arm developed sensory symptoms. One-time OAV101 IT demonstrated a statistically significant improvement in motor function compared with sham control. The overall safety findings were acceptable, with similar incidences of AEs, SAEs and AESI in the OAV101 IT and sham groups. Trial registration: ClinicalTrials.gov identifier: NCT05089656.Biochemistry, Genetics and Molecular BiologyMedicineArticleSCOPUS10.1038/s41591-025-04103-w2-s2.0-1050251276091546170X41360993