The North American Mitochondrial Disease Consortium (NAMDC)

北美线粒体是罕见疾病临床研究网络(RDCRN)的成员之一 疾病联盟(NAMDC)已经建立了一个由17个临床中心组成的网络，其使命是改善 诊断和护理，建立自然历史，支持翻译研究，调查 线粒体疾病的治疗。线粒体疾病在临床上和遗传学上都是 线粒体DNA(MtDNA)或核DNA原发突变引起的异质性疾病 (NDNA)。一个财团，与关键的患者权益倡导团体密切合作，包括 联合线粒体疾病基金会(UMDF)为这些复杂性提供了一种最佳方法 疾病。在NIH美国复苏和再投资法案(ARRA)的支持下， 作为U54奖项，NAMDC已经产生了一个实质性的研究基础设施：一个强大的 临床注册、生物信息库、教育和招募病人的网站，以及线粒体 疾病研究诊断标准，为临床项目和 审判。在这个坚实的基础上，19个以病人为导向的生产性项目已经萌芽，包括：4 自然历史研究；6项调查研究；9项试点研究。NAMDC培训方案已培训了5名 临床医生兼研究人员都在线粒体疾病研究中保持着非常活跃的状态。这 竞争续签申请提出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在NAMDC投资的劳动力中获得进一步回报。这个 研究项目是：1)扩大NAMDC临床注册/纵向研究和 生物信息库，对至少6种线粒体疾病进行了详细分析，并建立了新的注册表 至少3种疾病的自然历史研究；2)应用下一代测序来识别 约40%的NAMDC注册受试者的致病突变，其疾病的基因未定义 与线粒体疾病序列数据资源(MSeqDR)合作；3)开发 微创采集的组织中新的线粒体功能分析方法的应用 技术；4)扩展丙酮酸脱氢酶缺乏症的高级遗传学研究 增加了一项创新的生物标志物新生儿筛查计划和5)纵向扩展准入 脱氧核苷治疗TK2缺乏症的研究我们建议将我们的 将NAMDC奖学金转化为职业提升方案；启动新的试点研究；并过渡 NAMDC NIH向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.