Identifying Biomarkers of Spinal Muscular Atrophy for Further Development.
Identifying Biomarkers of Spinal Muscular Atrophy for Further Development.
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DOI：
10.3233/jnd-230054
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发表时间：
2023
影响因子：
3.3
通讯作者：
Jarecki, Jill
中科院分区：
文献类型：
--
作者：
Glascock, Jacqueline;Darras, Basil T.;Crawford, Thomas O.;Sumner, Charlotte J.;Kolb, Stephen J.;DiDonato, Christine;Elsheikh, Bakri;Howell, Kelly;Farwell, Wildon;Valente, Marta;Petrillo, Marco;Tingey, Jessica;Jarecki, Jill
脊髓性肌萎缩症（SMA）是由运动神经元生存基因1（SMN 1）的双等位基因隐性突变和运动神经元生存基因（SMN）蛋白表达水平降低引起的。脊髓中α运动神经元的变性导致进行性骨骼肌无力。疾病严重程度的广泛范围、不同的下降率和对获批疾病缓解治疗的异质性临床应答仍然知之甚少，限制了优化患者治疗的能力。验证可靠的生物标志物，可能支持早期诊断，告知疾病预后和治疗适用性，和/或确认对治疗的反应，代表SMA中显著未满足的需求。SMA多学科生物标志物工作组由11名相关领域的专家组成，旨在确定目前最有希望的候选生物标志物，确定关键的知识差距，并建议下一步验证SMA生物标志物。工作组采用改良的德尔菲法回答有关SMA候选生物标志物的问题。成员们参加了六轮重复调查，这些调查是在以往讨论的基础上设计的。工作组达成共识，认为神经丝（NF）是最适合进一步开发的候选生物标志物。会议确定了若干重要的知识差距，并提出了填补这些差距的下一步措施。NF是一种有前景的SMA生物标志物，具有预后、预测和药效学能力。工作组已经确定了继续努力验证NF作为SMA生物标志物所需的信息。
Spinal muscular atrophy (SMA) is caused by bi-allelic, recessive mutations of the survival motor neuron 1 (SMN1) gene and reduced expression levels of the survival motor neuron (SMN) protein. Degeneration of alpha motor neurons in the spinal cord causes progressive skeletal muscle weakness. The wide range of disease severities, variable rates of decline, and heterogenous clinical responses to approved disease-modifying treatment remain poorly understood and limit the ability to optimize treatment for patients. Validation of a reliable biomarker(s) with the potential to support early diagnosis, inform disease prognosis and therapeutic suitability, and/or confirm response to treatment(s) represents a significant unmet need in SMA. The SMA Multidisciplinary Biomarkers Working Group, comprising 11 experts in a variety of relevant fields, sought to determine the most promising candidate biomarker currently available, determine key knowledge gaps, and recommend next steps toward validating that biomarker for SMA. The Working Group engaged in a modified Delphi process to answer questions about candidate SMA biomarkers. Members participated in six rounds of reiterative surveys that were designed to build upon previous discussions. The Working Group reached a consensus that neurofilament (NF) is the candidate biomarker best poised for further development. Several important knowledge gaps were identified, and the next steps toward filling these gaps were proposed. NF is a promising SMA biomarker with the potential for prognostic, predictive, and pharmacodynamic capabilities. The Working Group has identified needed information to continue efforts toward the validation of NF as a biomarker for SMA.
影响因子：
3.1
作者：
Li, Jin-Yue;Dai, Yi;Sun, Xiao-Han;Ren, Hai-tao;Shen, Dong-chao;Yang, Xun-Zhe;Liu, Ming-Sheng;Cui, Li-Ying
通讯作者：
Cui, Li-Ying