Emerging therapies and challenges in spinal muscular atrophy.
Emerging therapies and challenges in spinal muscular atrophy.
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DOI：
10.1002/ana.24864
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发表时间：
2017-03
影响因子：
11.2
通讯作者：
Kiernan MC
中科院分区：
文献类型：
--
作者：
Farrar MA;Park SB;Vucic S;Carey KA;Turner BJ;Gillingwater TH;Swoboda KJ;Kiernan MC
脊髓性肌萎缩症（SMA）是一种遗传性神经退行性疾病，其严重程度从进行性婴儿麻痹和过早死亡（I型）到有限的运动神经元损失和正常预期寿命（IV型）不等。如果没有疾病修饰疗法，对患者及其家属的影响将是深远的。随着对SMA分子基础、疾病发病机制、自然史的进一步了解，以及对标准化治疗对结局影响的认识，在开发新型治疗策略方面取得了进展，并进行了总结。治疗策略的管道进行评估，从SMN 1基因替代SMN 2编码的转录物的调制，神经保护，扩大外周靶点，包括肌肉。随着初步试验数据的出现，可以合理预期SMA治疗前景将发生重大变化。症状前诊断和筛查项目的进展将是至关重要的，正在进行的试点新生儿筛查研究将促进临床前诊断。疾病改善疗法的发展需要监测计划来确定长期影响，仔细评估联合治疗，并进一步加速支持性治疗的改善。在即将到来的临床试验结果之前，我们考虑了与为所有患者实施新疗法相关的挑战和争议，并为该领域准备进入新疗法时代做好了准备。神经学年鉴2017;81：355-368
Spinal muscular atrophy (SMA) is a hereditary neurodegenerative disease with severity ranging from progressive infantile paralysis and premature death (type I) to limited motor neuron loss and normal life expectancy (type IV). Without disease‐modifying therapies, the impact is profound for patients and their families. Improved understanding of the molecular basis of SMA, disease pathogenesis, natural history, and recognition of the impact of standardized care on outcomes has yielded progress toward the development of novel therapeutic strategies and are summarized. Therapeutic strategies in the pipeline are appraised, ranging from SMN1 gene replacement to modulation of SMN2 encoded transcripts, to neuroprotection, to an expanding repertoire of peripheral targets, including muscle. With the advent of preliminary trial data, it can be reasonably anticipated that the SMA treatment landscape will transform significantly. Advancement in presymptomatic diagnosis and screening programs will be critical, with pilot newborn screening studies underway to facilitate preclinical diagnosis. The development of disease‐modifying therapies will necessitate monitoring programs to determine the long‐term impact, careful evaluation of combined treatments, and further acceleration of improvements in supportive care. In advance of upcoming clinical trial results, we consider the challenges and controversies related to the implementation of novel therapies for all patients and set the scene as the field prepares to enter an era of novel therapies. Ann Neurol 2017;81:355–368