Clinic for Special Children, Strasburg, PA, USA.
Penn Medicine-Lancaster General Hospital, Lancaster, PA, USA.
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.
大多数携带双等位基因 SMN1 缺失和三个 SMN2 拷贝的儿童会发展为脊髓性肌萎缩症（SMA）2 型。SPR1NT（NCT03505099）是一项三期、多中心、单臂试验，研究了onasemnogene abeparvovec 对出生后六周内接受治疗的双等位基因 SMN1 突变的有症状前儿童的疗效和安全性。在 15 名发病前接受治疗且携带三个 SMN2 拷贝的儿童中，所有儿童在 24 个月前均能独立站立（P<0.0001；14 名在正常发育窗口内），14 名儿童能独立行走（P<0.0001；11 名在正常发育窗口内）。所有儿童在 14 个月时无需永久通气即可存活；10 名（67%）儿童在 24 个月时无需喂养支持即可维持体重（≥WHO 第 3 百分位）；且无一例需要营养或呼吸支持。研究者认为，没有严重不良事件与治疗相关。Onasemnogene abeparvovec 对有患 SMA 2 型风险的有症状前婴儿是有效且耐受良好的，这突显了早期识别和干预的紧迫性。
