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）：北美线粒体疾病财团（NAMDC）的稀有疾病临床研究网络（RDCRN）的成员已建立了一个由18个临床中心组成的网络，以改善诊断，建立自然史和研究线粒体疾病的治疗。由于线粒体DNA（mtDNA）或核DNA（NDNA）的一级突变，线粒体疾病在临床和遗传上是异质性的。只有通过一个财团与患者倡导团体密切合作。线粒体疾病基金会（UMDF）和肌肉营养不良协会，我们可以解决这些复杂疾病。在NIH American Recovery and Recovery Act（ARRA）赠款和U54奖2年的支持下，NAMDC已经制作了一项强大的临床注册表/临床纵向研究，其中有425多名已包含的患者，一个Biorespository，一个Biorespository，Biorespository，一个用于患者的教育和招聘的网站，以及Mitochrial疾病疾病研究诊断标准，以及其他诊所研究的基础。从这个公司基础上，有生产力的以患者为导向的项目已经发芽，其中包括3项自然史研究（线粒体神经胃肠道症状症状（MNGIE）（MNGIE），Alpers综合征和Pearson综合征，这是一项超高野外核磁性共体的试验性研究，以评估肌肉和脑脑中脑中脑酸和脑含量的代谢，以评估肌肉酸和脑含量。情节（Melas）以及广泛的初步工作（包括成功的FDA IND应用程序）为同种异体造血干细胞移植（AHSCT）的创新自适应安全研究奠定了基础。提议扩大NAMDC临床注册中心/纵向研究和生物现象；完成MNGIE AHSCT安全研究；启动丙酮酸脱氢酶复合物缺乏的自然史和晚期遗传学研究；启动新的试点研究，包括一项第一阶段的瓜氨酸疗法FR Melas；继续NAMDC临床奖学金培训计划；并开发新的研究和合作范围，包括研究线粒体疾病患者中营养补充剂的使用以及与线粒体疾病序列数据资源（MSEQDR）财团的密切合作。