NAMDC: Overall Research Plan

NAMDC：总体研究计划

• 批准号: 9353470
• 负责人: MICHIO HIRANO
• 金额: $ 108.85万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9353470
• 关键词: Address; Allogenic; Alpers' Syndrome; American; Award; Brain; Caring; Citrulline; Clinical; Clinical Research; Clinical Trials; Collaborations; Complex; DNA; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostics Research; Disease; Dose; Education; Enrollment; Fellowship; Foundations; Genetic study; Grant; Hematopoietic Stem Cell Transplantation; Industry; Institutional Review Boards; Investigation; Laboratory Research; Link; Longitudinal Studies; MELAS Syndrome; MNGIE; Mission; Mitochondria; Mitochondrial DNA; Mitochondrial Diseases; Multicenter Studies; Muscle; Muscular Dystrophies; Mutation; Natural History; Nitric Oxide; Nuclear; Nuclear Magnetic Resonance; Parkinson Disease; Pathogenesis; Patient Recruitments; Patients; Phase; Pilot Projects; Protocols documentation; Pyruvate Dehydrogenase Complex Deficiency Disease; Rare Diseases; Recovery; Registries; Research; Research Infrastructure; Research Methodology; Research Personnel; Rewards; Role; Supplementation; Syndrome; Time; Training; Training Programs; United States National Institutes of Health; Work; base; biobank; data resource; dietary supplements; human disease; improved; innovation; member; mitochondrial dysfunction; next generation; patient advocacy group; patient oriented; patient oriented research; phase 1 study; public health relevance; research study; safety study; web site

DESCRIPTION (provided by applicant): A member of the Rare Diseases Clinical Research Network (RDCRN), the North American Mitochondrial Disease Consortium (NAMDC) has established a network of 18 clinical centers to improve the diagnosis, establish the natural history, and investigate treatment of mitochondrial diseases. Mitochondrial diseases are clinically and genetically heterogeneous due to primary mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Only through a consortium, acting in close collaboration with the patient advocacy groups. United Mitochondrial Disease Foundation (UMDF) and Muscular Dystrophy Association, can we address these complex diseases. With support of an NIH American Recovery and Recovery Act (ARRA) grant and 2 years of a U54 award, NAMDC has already produced a powerful Clinical Registry/Clinical Longitudinal Study with over 425 enrolled patients, a Biorespository, a website for education and recruitment of patients, and mitochondrial disease Research Diagnostic Criteria, which are the foundation for additional clinical research studies. From this firm base, productive patient-oriented projects have already sprouted including 3 natural history studies (mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), Alpers syndrome, and Pearson syndrome, a pilot study of ultra-high field nuclear magnetic resonance to assess metabolites in muscle and brain of patients with mitochondrial encephalopathy lactic acidosis and stroke-like episodes (MELAS), as well as extensive preliminary work (including a successful FDA IND application) setting the stage for an innovative adaptive safety study of allogeneic hematopoietic stem cell transplantation (AHSCT) for MNGIE. The NAMDC training program has been established to train the next generation of clinician investigators. Additional work is required to reap the rewards of the labor invested in this consortium. In this application, we propose to expand the NAMDC Clinical Registry/Longitudinal Study and Biorepository; to apply and refine the Research Diagnostic Criteria; to continue on-going natural history studies; to complete the MNGIE AHSCT safety study; to launch a natural history and advanced genetics study of pyruvate dehydrogenase complex deficiency; to initiate new pilot studies including a phase I study of citrulline therapy fr MELAS; to continue the NAMDC clinical fellowship training program; and to develop new lines of research and collaborations including investigation of use of nutritional supplements among mitochondrial disease patients and close collaborations with the mitochondrial disease sequence data resource (MSeqDR) consortium.

描述（由申请人提供）：作为罕见疾病临床研究网络 (RDCRN) 的成员，北美线粒体疾病联盟 (NAMDC) 建立了一个由 18 个临床中心组成的网络，以改进线粒体疾病的诊断、建立自然史并研究治疗方法。由于线粒体 DNA (mtDNA) 或核 DNA (nDNA) 的原发突变，线粒体疾病在临床和遗传上具有异质性。只能通过一个联盟，与患者权益团体密切合作。联合线粒体疾病基金会 (UMDF) 和肌营养不良协会，我们可以解决这些复杂的疾病吗？在 NIH 美国康复与恢复法案 (ARRA) 拨款和 2 年 U54 奖项的支持下，NAMDC 已经制定了一项强大的临床登记/临床纵向研究，涵盖了超过 425 名入组患者、生物储存库、患者教育和招募网站以及线粒体疾病研究诊断标准，这些都是其他临床研究的基础。在这个坚实的基础上，富有成效的以患者为导向的项目已经萌芽，包括 3 项自然史研究（线粒体神经胃肠道脑肌病 (MNGIE)、阿尔珀斯综合征和皮尔逊综合征，这是一项超高场核磁共振试点研究，用于评估线粒体脑病、乳酸性酸中毒和中风样患者肌肉和大脑中的代谢物） 事件（MELAS），以及广泛的前期工作（包括成功的 FDA IND 申请）为 MNGIE 异基因造血干细胞移植（AHSCT）的创新适应性安全性研究奠定了基础。 NAMDC 培训计划的建立是为了培训下一代临床研究人员。需要进行额外的工作才能获得对该联盟的劳动投入的回报。在这个应用程序中，我们 建议扩大 NAMDC 临床注册/纵向研究和生物样本库；应用和完善研究诊断标准；继续正在进行的自然历史研究；完成 MNGIE AHSCT 安全性研究；开展丙酮酸脱氢酶复合物缺乏症的自然史和高级遗传学研究；启动新的试点研究，包括瓜氨酸疗法 fr MELAS 的 I 期研究；继续 NAMDC 临床进修培训计划；开发新的研究和合作领域，包括调查线粒体疾病患者营养补充剂的使用情况以及与线粒体疾病序列数据资源 (MSeqDR) 联盟的密切合作。