Kawai Mitsuru
National Hospital Organization, Higashisaitama National Hospital.
Rinsho Shinkeigaku. 2009 Nov;49(11):863-6. doi: 10.5692/clinicalneurol.49.863.
About 20 years have passed since the discovery of the causative protein of Duchenne muscular dystrophy, in 1987, and treatments targeting causative factors such as exon skipping, read-through of stop codons, and the upregulation of utrophin are approaching practical levels. In Japan, also, clinical trials are planned as the final stage of treatment development. In this field, an appropriate outcome measure has not been established due to the lack of experience in clinical trials. Treatments for muscular dystrophy are deemed effective only when increases in the muscle mass and muscle strength and improvements in the ADL and QOL as well as biological marker levels at target points have been demonstrated. The Muscular Dystrophy Clinical Study Group has addressed the development of these evaluation methods since 2002. Also, as treatments for muscular dystrophy being developed today are so-called tailor-made treatments aimed at specific mutations, a system that facilitates identification of the type and site of mutation in each individual must be prepared. The Gene Analysis Center was only just established in the National Center of Neurology and Psychiatry in 2009. Also, it is expected to be difficult to secure a sufficient number of subjects to start a clinical trial in a short period. Therefore, the Registry of Muscular Dystrophy (REMUDY), a system for the registration of patients with muscular dystrophy including their clinical and genetic information was implemented. This system, which provides information concerning the number of patients required by the protocol to researchers and pharmaceutical companies and the latest information regarding the development of treatments to patients, is expected to serve as a prototype for the establishment of the basis of clinical trials against rare diseases.
自1987年杜氏肌营养不良症致病蛋白被发现以来，大约20年过去了，针对致病因素的治疗方法，如外显子跳跃、终止密码子通读和上调抗肌萎缩蛋白，正逐渐接近实际应用水平。在日本，治疗开发的最后阶段也已计划开展临床试验。在该领域，由于缺乏临床试验经验，尚未建立合适的疗效评估指标。只有当肌肉质量和力量增加、日常生活活动能力和生活质量改善以及靶点处生物标志物水平提高得到证实时，肌营养不良症的治疗才被认为是有效的。自2002年以来，肌营养不良症临床研究小组一直在致力于这些评估方法的开发。此外，由于目前正在开发的肌营养不良症治疗方法是针对特定突变的所谓定制治疗，因此必须建立一个便于识别每个个体突变类型和位点的系统。基因分析中心于2009年才在国立精神神经医疗研究中心刚刚成立。此外，预计在短时间内难以确保获得足够数量的受试者来启动临床试验。因此，实施了肌营养不良症登记系统（REMUDY），该系统用于登记肌营养不良症患者及其临床和遗传信息。该系统为研究人员和制药公司提供方案所需患者数量的信息，并为患者提供治疗进展的最新信息，有望成为建立罕见病临床试验基础的原型。
