Porphyria Rare Disease Clinical Research Consortium (RDCRC)

描述(由申请者提供)：我们建议继续和扩大卟啉症联合会(PC)的临床研究和培训计划，该联合会目前是罕见疾病临床研究网络(RDCRN)的一个联合体，专注于血红素生物合成的先天错误，即卟啉症。该委员会汇集了六个地区中心的高级卟啉病专家、美国唯一的卟啉症患者倡导和支持组织美国卟啉病基金会(APF)以及对改善这些不同疾病的诊断和/或开发新疗法感兴趣的生物制药公司的互补优势。首席研究员和行政主任将分别是西奈山伊坎医学院(MSSM)的罗伯特·J·德斯尼克博士和加尔维斯顿德克萨斯大学医学分校的卡尔·E·安德森医学博士。其他四名联盟董事是加州大学旧金山分校(UCSF)D·蒙哥马利·比塞尔医学博士、阿拉巴马大学伯明翰分校(UAB)约瑟夫·R·布鲁默医学博士、卡罗莱纳州医疗保健系统(CHS)医学博士赫伯特·L·邦科夫斯基(Herbert L.Bonkovsky)和犹他大学(Utah University)博士约翰·菲利普斯(John Phillips)。这些卟啉病专家组成了一支由翻译和临床研究人员组成的互动和跨学科团队，他们拥有积极的基础和临床研究计划，在培训年轻研究人员方面有良好的记录，以及国际公认的临床专业知识。在过去的四年里，他们一直作为一个有效的团队合作，以实现每个项目的进度报告中记录的筹委会的最初目标。在不到三年的时间里，PC招募了450多名患者参加纵向研究(LS)，以记录每个门静脉症的自然历史，并启动了其他六项临床研究或试验， 和一个试点/示范项目。我们将继续通过联络登记处、预科医生和医生转介，以及建立外展诊所，招收病人参加LS和其他研究。此外，我们将继续培训下一代的门静脉疾病专家，并由患者和产业界捐赠150万美元的配对补助金。新的研究将集中在急性肝性卟啉症上，包括一个寻找安全新药的项目，以及在Panhematin(R)和一种新的RNA干扰疗法进行临床试验之前的一项深入观察研究。试点/示范计划将包括对卟啉病候选修饰基因的调查，基于Skype的焦点小组，以及肝脏ALAS1的外切体分析。这些研究将导致对这些疾病进行更有效的管理和治疗。

DESCRIPTION (provided by applicant): We propose to continue and expand the clinical research and training programs of the Porphyrias Consortium (PC), a currently funded Consortium of the Rare Disease Clinical Research Network (RDCRN) that focuses on the inborn errors of heme biosynthesis, the porphyrias. The PC has brought together the complementary strengths of the senior porphyria experts at six regional centers; the American Porphyria Foundation (APF), the only US porphyria patient advocacy and support group; and biopharmaceutical companies interested in improving diagnosis and/or developing novel therapies for these diverse diseases. The Principal Investigator and Administrative Director will be Robert J. Desnick, PhD, MD, Icahn School of Medicine at Mount Sinai (MSSM) and Karl E. Anderson, MD, University of Texas Medical Branch, Galveston, respectively. The other four Consortium Directors are D. Montgomery Bissell, MD, University of California at San Francisco (UCSF); Joseph R. Bloomer, MD, University of Alabama at Birmingham (UAB); Herbert L. Bonkovsky, MD, Carolinas HealthCare System (CHS); and John Phillips, PhD, University of Utah (UoU). These porphyria experts form an interactive and interdisciplinary team of translational and clinical investigators who have active basic and clinical porphyria research programs, strong track records for training young investigators, and internationally recognized clinical expertise. For the past four years, they have worked as an effective team to accomplish the original objectives of the PC as documented in the progress reports for each project. The PC recruited over 450 patients in less than three years to the Longitudinal Study (LS) to document the natural history of each porphyria, and initiated six other clinical studies or trials, and a pilot/demonstration project. We will continue to enroll patients into the LS and other studies through the Contact Registry, APF and physician referrals, and the establishment of Outreach Clinics. In addition, we will continue training the next generation of porphyria experts, supported by $1.5 million in matching grants donated by patients and industry. New studies will focus on the acute hepatic porphyrias, including a project to identify safe new drugs and an in-depth observational study prior to clinical trials of Panhematin(r) and a novel RNA interference therapy. The pilot/demonstration program will include investigation of porphyria candidate modifier genes, Skype-based focus groups, and an exosome assay for hepatic ALAS1. These studies should lead to more effective management and treatment of these diseases.