Swoboda Kathryn J, Kissel John T, Crawford Thomas O, Bromberg Mark B, Acsadi Gyula, D'Anjou Guy, Krosschell Kristin J, Reyna Sandra P, Schroth Mary K, Scott Charles B, Simard Louise R
Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
J Child Neurol. 2007 Aug;22(8):957-66. doi: 10.1177/0883073807305665.
Spinal muscular atrophy is one of the most heterogeneous of the single-gene neuromuscular disorders. The broad spectrum of severity, with onset from the prenatal period to adulthood, presents unique challenges in the design and implementation of clinical trials. The clinical classification of subjects into severe (type 1), intermediate (type 2), and mild (type 3) subtypes has proved useful both in enhancing communication among clinicians internationally and in forging the collaborative development of outcome measures for clinical trials. Ideally, clinical trial design in spinal muscular atrophy must take into account the spinal muscular atrophy type, patient age, severity-of-affection status, nature of the therapeutic approach, timing of the proposed intervention relative to disease progression, and relative homogeneity of the cohort to be studied. Following is an overview of the challenges and opportunities, current and future therapeutic strategies, and progress to date in clinical trials in spinal muscular atrophy.
脊髓性肌萎缩症是单基因神经肌肉疾病中异质性最强的疾病之一。其严重程度范围广泛，发病时间从胎儿期到成年期不等，这给临床试验的设计和实施带来了独特的挑战。将受试者临床分类为重度（1型）、中度（2型）和轻度（3型）亚型，已证明在加强国际临床医生之间的交流以及推动临床试验结局指标的协作开发方面都很有用。理想情况下，脊髓性肌萎缩症的临床试验设计必须考虑脊髓性肌萎缩症的类型、患者年龄、病情严重程度、治疗方法的性质、拟进行干预相对于疾病进展的时间，以及拟研究队列的相对同质性。以下是脊髓性肌萎缩症临床试验中面临的挑战与机遇、当前和未来的治疗策略以及迄今为止所取得的进展概述。
