The North American Mitochondrial Disease Consortium (NAMDC)

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）已建立了由17个临床中心组成的网络，其使命是改善 诊断和护理，建立自然史，支持转化研究，并调查 线粒体疾病的治疗。线粒体疾病在临床上和遗传学上 由于线粒体DNA（mtDNA）或核DNA的原发性突变引起的异质性疾病 （nDNA）。一个与主要的患者倡导团体密切合作的联盟，包括 联合线粒体疾病基金会（UMDF），提供了一个最佳的方法，这些复杂的 疾病在NIH美国复苏和再投资法案（ARRA）拨款的支持下， 作为U 54奖，NAMDC已经产生了大量的研究基础设施： 临床登记处，生物储存库，用于教育和招募患者的网站，以及线粒体 疾病研究诊断标准，为临床项目提供必要的基础， 审判在这个坚实的基础上，已经开展了19个富有成效的面向患者的项目，包括： 自然历史研究; 6项调查研究; 9项试点研究。NAMDC培训方案培训了5名 所有这些人都在线粒体疾病研究中非常活跃。这 竞争性续签申请提出5个主要研究项目和一个新的职业提升 该计划将扩大并从迄今为止在NAMDC投入的劳动力中获得更多回报。的 研究项目包括：1）扩大NAMDC临床登记/纵向研究， 详细分析至少6种线粒体疾病的生物储存库和基于新登记册的 至少3种疾病的自然史研究; 2）应用下一代测序技术， 在约40%的NAMDC登记研究受试者中发生致病突变，这些受试者的疾病在遗传学上是不确定的 与线粒体疾病序列数据资源（MSeqDR）合作; 3）开发 以及在通过微创方法收集的组织中利用新的线粒体功能测定 技术; 4）丙酮酸脱氢酶缺乏症的先进遗传学研究的扩展， 增加了创新的生物标志物新生儿筛查计划，以及5）纵向扩展访问 脱氧核苷治疗胸苷激酶2缺陷症研究我们建议将我们的 NAMDC研究金用于职业提升计划;启动新的试点研究;以及过渡到 NAMDC国家卫生研究院为更广泛的资金来源提供财政支持。

A member of the Rare Diseases Clinical Research Network (RDCRN), the North American Mitochondrial Disease Consortium (NAMDC) has established a network of 17 clinical centers with a mission to improve the diagnosis and care, establish the natural history, support translational research, and investigate treatment of mitochondrial diseases. Mitochondrial diseases are clinically and genetically heterogeneous disorders due to primary mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). A consortium, acting in close collaboration with the key patient advocacy groups, including the United Mitochondrial Disease Foundation (UMDF), provides an optimal approach to these complex diseases. With support of an NIH American Recovery and Reinvestment Act (ARRA) grant and 7 years of a U54 award, NAMDC has already generated produced a substantial research infrastructure: a powerful Clinical Registry, a Biorepository, a website for education and recruitment of patients, and mitochondrial disease Research Diagnostic Criteria, which provide an essential foundation for clinical projects and trials. From this firm base, 19 productive patient-oriented projects have already sprouted, including: 4 natural history studies; 6 survey studies; and 9 pilot studies. The NAMDC training program has trained 5 clinician-investigators all of whom remain remarkably active in mitochondrial disease research. This competitive renewal application proposes 5 major Research Projects and a new Career Enhancement program which will expand and reap further rewards from the labor invested to date in NAMDC. The Research Projects are: 1) An expansion of the NAMDC Clinical Registry/Longitudinal Study and Biorepository with detailed analyses of at least 6 mitochondrial disorders and novel registry-based natural history studies of at least 3 diseases; 2) Application of next-generation sequencing to identify causative mutations in the ~40% of NAMDC Registry subjects whose diseases are genetically undefined in collaboration with the Mitochondrial disease SEQuence Data Resource (MSeqDR); 3) Development and utilization of new mitochondrial functional assays in tissues collected via minimally invasive techniques; 4) Extension of an advanced genetics study of pyruvate dehydrogenase deficiency with addition of an innovative biomarker newborn screening program and 5) A longitudinal expanded access study of deoxynucleoside therapy for thymidine kinase 2 (TK2) deficiency. We propose to transform our NAMDC Fellowship into a Career Enhancement program; to initiate new pilot studies; and to transition NAMDC NIH financial support to a broader array of funding sources.