Telethon Kids Institute, Centre for Child Health Research, The University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia.
University of Sydney, Sydney, NSW, Australia.
Orphanet J Rare Dis. 2022 Mar 4;17(1):108. doi: 10.1186/s13023-022-02240-w.
Rett syndrome is associated with severe functional impairments and many comorbidities, each in urgent need of treatments. Mutations in the MECP2 gene were identified as causing Rett syndrome in 1999. Over the past 20 years there has been an abundance of preclinical research with some studies leading to human clinical trials. Despite this, few viable therapeutic options have emerged from this investment of effort. Reasons for this lack of success as they relate both to preclinical research and the clinical trial landscape are discussed. Considering what needs to be done to promote further success in the field, we take a positive and constructive approach and introduce the concept of clinical trial readiness and its necessary ingredients for Rett syndrome. These include: listening to the needs of families; support from advocacy groups; optimising use of existing clinic infrastructures and available natural history data; and, finally, the validation of existing outcome measures and/or the development and validation of new measures. We conclude by reiterating the need for a collaborative and coordinated approach amongst the many different stakeholder groups and the need to engage in new types of trial design which could be much more efficient, less costly and much less burdensome on families.
雷特综合征与严重的功能障碍和许多合并症有关，每种疾病都急需治疗。1999 年，MECP2 基因突变被确定为导致雷特综合征的原因。在过去的 20 年里，有大量的临床前研究，其中一些研究导致了人体临床试验。尽管如此，从这项努力中也只出现了少数可行的治疗选择。造成这种缺乏成功的原因既与临床前研究有关，也与临床试验领域有关。考虑到需要做些什么来促进该领域的进一步成功，我们采取了积极和建设性的方法，并引入了临床试验准备的概念及其对雷特综合征的必要成分。这些包括：倾听家庭的需求；来自宣传团体的支持；优化利用现有的临床基础设施和可用的自然病史数据；最后，验证现有的结果测量方法，或开发和验证新的测量方法。我们最后重申，需要在众多不同利益相关者群体之间采取协作和协调的方法，需要参与新类型的试验设计，这种设计可能更有效率、成本更低、对家庭的负担也更小。
