Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe)

项目摘要/摘要 ALS和相关疾病的临床研究用于治疗开发(CREATE)联盟是罕见的 疾病临床研究联盟(RDCRC)，组成国家卫生研究院Rare的一部分 疾病临床研究网络(RDCRN)。CREATE包括一个多学科的临床医生小组， 科学家、教育工作者、患者倡导团体和其他战略合作伙伴，旨在推动治疗 肌萎缩侧索硬化症(ALS)和包括进展性疾病在内的相关疾病的进展 肌萎缩(PMA)、原发性侧索硬化症(PLS)、额颞叶痴呆(FTD)、多系统 蛋白质病(MSP)和遗传性痉挛截瘫(HSP)。我们认识到治疗的障碍 发育是多因素的，包括：(A)病因和生物异质性；(B)表型 异质性；(C)用于早期和中期临床试验的现有临床结果衡量标准的局限性； (D)缺乏已被确认为“适合用途”的生物标志物)；(E)相对较晚的阶段 出现症状，作出诊断，开始治疗；和(F)患者的变异率(通常较低) 参与临床研究。Create研究人员正在进行一系列临床试验 准备活动，旨在克服这些障碍，从而推动治疗开发 这组罕见的疾病。此外，Create的目标是促进和支持 肌萎缩侧索硬化症及相关疾病领域；开发和传播资源，如创建生物资源库和 我们基于电子健康记录的ALS工具包，对更广泛的科学界有价值；更低 患者参与研究的障碍；培养和提高年轻临床研究人员的职业生涯 和致力于这组罕见疾病研究的转化型科学家；并让普通人和 科学界利益相关者建立伙伴关系，努力为患者开发治疗方法 受这些罕见疾病的折磨。

Project Summary / Abstract The Clinical Research in ALS and related disorders for Therapy Development (CReATe) Consortium is a Rare Diseases Clinical Research Consortium (RDCRC) that forms part of the National Institutes of Health Rare Diseases Clinical Research Network (RDCRN). CReATe comprises a multi-disciplinary group of clinicians, scientists, educators, patient advocacy groups and other strategic partners, and aims to advance therapeutic development for patients with amyotrophic lateral sclerosis (ALS) and related disorders including progressive muscular atrophy (PMA), primary lateral sclerosis (PLS), frontotemporal dementia (FTD), multisystem proteinopathy (MSP), and hereditary spastic paraplegia (HSP). We recognize that the obstacles to therapeutic development are multifactorial and include: (a) etiological and biological heterogeneity; (b) phenotypic heterogeneity; (c) limitations of existing clinical outcome measures for use in early-to-mid phase clinical trials; (d) a paucity of biomarkers that have been validated as “fit for purpose”); (e) the relatively late stage at which symptoms appear, diagnosis is made, and treatment is initiated; and (f) variable (often low) rates of patient participation in clinical research studies. CReATe investigators are engaged in a range of clinical trial readiness activities that aim to overcome these obstacles, and to thereby advance therapeutic development for this group of rare diseases. In addition, CReATe aims to promote and support collaborative research in the field of ALS and related disorders; develop and disseminate resources such as the CReATe Biorepository and our electronic health record-based ALS Toolkit that are of value to the broader scientific community; lower barriers to patient participation in research; cultivate and enhance the careers of young clinical investigators and translational scientists dedicated to the study of this group of rare diseases; and engage both lay- and scientific-community stakeholders in a partnership that fosters efforts to develop treatments for patients afflicted with these rare diseases.