Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial.
Onasemnogene abeparvovec for presymptomatic infants with three copies of SMN2 at risk for spinal muscular atrophy: the Phase III SPR1NT trial.
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DOI：
10.1038/s41591-022-01867-3
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发表时间：
2022-07
期刊：
影响因子：
82.9
通讯作者：
Macek, Thomas A.
中科院分区：
文献类型：
--
作者：
Strauss, Kevin A.;Farrar, Michelle A.;Muntoni, Francesco;Saito, Kayoko;Mendell, Jerry R.;Servais, Laurent;McMillan, Hugh J.;Finkel, Richard S.;Swoboda, Kathryn J.;Kwon, Jennifer M.;Zaidman, Craig M.;Chiriboga, Claudia A.;Iannaccone, Susan T.;Krueger, Jena M.;Parsons, Julie A.;Shieh, Perry B.;Kavanagh, Sarah;Wigderson, Melissa;Tauscher-Wisniewski, Sitra;McGill, Bryan E.;Macek, Thomas A.
大多数带有双等位SMN1缺失和3个SMN1拷贝的儿童发展为2型脊髓性肌萎缩症(SMA)。SPR1NT(NCT03505099)是一项III期多中心单臂试验，研究了在出生后6周内治疗具有双等位SMN1突变的症状前儿童的疗效和安全性。在症状出现前接受治疗的15名儿童中，所有儿童在24个 月前均独立站立(P <； 0.0001；14例在正常发育窗内)，14例独立行走(P <； 0.0001；11例在正常发育窗内)。所有患者在14个 月时均在没有永久机械通气的情况下存活；10名(67%)在24个月内没有喂养支持的情况下维持体重(≥第3百分位数)；没有人需要营养或呼吸支持。调查者认为没有严重的不良反应与治疗有关。Onasemnogene abepparvovec对有SMA 2型风险的症状前婴儿有效且耐受性良好，强调了早期识别和干预的紧迫性。对于有三个SMN1副本的婴儿有患1型脊髓性肌萎缩症(SMA)的风险，onasemnogene bebeparvovec可以改善无需呼吸机的存活率和营养/呼吸独立性，并使运动发育与没有SMA的健康儿童没有区别。
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. For infants with three copies of SMN1 at risk for spinal muscular atrophy (SMA) type 1, onasemnogene abeparvovec improves ventilator-free survival and nutritional/respiratory independence and allows motor development indistinguishable from healthy children without SMA.
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影响因子：
3.3
作者：
Friese J;Geitmann S;Holzwarth D;Müller N;Sassen R;Baur U;Adler K;Kirschner J
通讯作者：
Kirschner J
影响因子：
4.2
作者：
Day JW;Mendell JR;Mercuri E;Finkel RS;Strauss KA;Kleyn A;Tauscher-Wisniewski S;Tukov FF;Reyna SP;Chand DH
通讯作者：
Chand DH
影响因子：
9.9
作者：
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通讯作者：
De Vivo, Darryl C.
影响因子：
3.5
作者：
Coovert, DD;Le, TT;Burghes, AHM
通讯作者：
Burghes, AHM
影响因子：
2.8
作者：
De Vivo, Darryl C.;Bertini, Enrico;Farwell, Wildon
通讯作者：
Farwell, Wildon