Natural history of infantile-onset spinal muscular atrophy.
Natural history of infantile-onset spinal muscular atrophy.
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婴儿发作的脊柱肌肉萎缩的自然历史。
DOI：
10.1002/ana.25101
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发表时间：
2017-12
影响因子：
11.2
通讯作者：
NeuroNEXT Clinical Trial Network on behalf of the NN101 SMA Biomarker Investigators
中科院分区：
文献类型：
--
作者：
Kolb SJ;Coffey CS;Yankey JW;Krosschell K;Arnold WD;Rutkove SB;Swoboda KJ;Reyna SP;Sakonju A;Darras BT;Shell R;Kuntz N;Castro D;Parsons J;Connolly AM;Chiriboga CA;McDonald C;Burnette WB;Werner K;Thangarajh M;Shieh PB;Finanger E;Cudkowicz ME;McGovern MM;McNeil DE;Finkel R;Iannaccone ST;Kaye E;Kingsley A;Renusch SR;McGovern VL;Wang X;Zaworski PG;Prior TW;Burghes AHM;Bartlett A;Kissel JT;NeuroNEXT Clinical Trial Network on behalf of the NN101 SMA Biomarker Investigators
婴儿发病的脊髓性肌萎缩症（SMA）是婴儿死亡最常见的遗传原因，通常导致2岁前死亡。在这一人群中进行临床试验需要了解疾病进展和确定有意义的生物标志物，以加速治疗开发和预测结果。一项纵向、多中心、前瞻性自然史研究招募了26名SMA婴儿和27名小于6个月的对照婴儿。招募在nind资助的NeuroNEXT网络内的14个中心进行，为期21个月。在6个月前以及6、9、12、18和24个月的进展阶段，对婴儿运动功能量表（TIMPSI、chop - intent和AIMS）和假定的生理和分子生物标志物进行评估，分析运动功能与生物标志物和风险比之间的相关性。运动功能评分（MFS）和CMAP在SMA婴儿中迅速下降，而所有健康婴儿的MFS迅速增加。在SMA婴儿中发现TIMPSI和CMAP之间的相关性。首次研究访问时的TIMPSI与SMA婴儿死亡或永久性有创通气的联合终点风险相关。对携带2份SMN2的SMA婴儿的生存至联合终点的事后分析显示，死亡时的中位年龄为8个月（95%CI: 6,17）。这些SMA的数据和对照结果指标描述了婴儿发病SMA临床试验中有意义的变化。NeuroNEXT提供“真实世界”的前瞻性自然历史数据集，以加速罕见疾病的公共和私人药物开发计划的能力和效用得到了证明。
Infantile-onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death prior to age 2. Clinical trials in this population require an understanding of disease progression and identification of meaningful biomarkers to hasten therapeutic development and predict outcomes. A longitudinal, multi-center, prospective natural history study enrolled 26 SMA infants, and 27 control infants less than six months of age. Recruitment occurred at 14 centers over 21 months within the NINDS-sponsored NeuroNEXT Network. Infant motor function scales (TIMPSI, CHOP-INTEND and AIMS) and putative physiologic and molecular biomarkers were assessed prior to 6 months of age and at 6, 9, 12, 18 and 24-months with progression, correlations between motor function and biomarkers and hazard ratios were analyzed. Motor function scores (MFS) and CMAP decreased rapidly in SMA infants, whereas MFS in all healthy infants rapidly increased. Correlations were identified between TIMPSI and CMAP in SMA infants. TIMPSI at first study visit was associated with risk of combined endpoint of death or permanent invasive ventilation in SMA infants. Post hoc analysis of survival to combined endpoint in SMA infants with 2 copies of SMN2 indicated a median age of 8 months at death (95%CI: 6,17). These data of SMA and control outcome measures delineates meaningful change in clinical trials in infantile-onset SMA. The power and utility of NeuroNEXT to provide “real world”, prospective natural history data sets to accelerate public and private drug development programs for rare disease is demonstrated.
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影响因子：
11.2
作者：
Duque, Sandra I.;Arnold, W. David;Odermatt, Philipp;Li, Xiaohui;Porensky, Paul N.;Schmelzer, Leah;Meyer, Kathrin;Kolb, Stephen J.;Schuemperli, Daniel;Kaspar, Brian K.;Burghes, Arthur H. M.
通讯作者：
Burghes, Arthur H. M.
影响因子：
30.8
作者：
Lefebvre, S;Burlet, P;Melki, J
通讯作者：
Melki, J
影响因子：
9.9
作者：
Finkel, Richard S.;McDermott, Michael P.;De Vivo, Darryl C.
通讯作者：
De Vivo, Darryl C.
影响因子：
2.8
作者：
Glanzman, A. M.;Mazzone, E.;Finkel, R. S.
通讯作者：
Finkel, R. S.
影响因子：
3.5
作者：
Coovert, DD;Le, TT;Burghes, AHM
通讯作者：
Burghes, AHM