Porphyria Rare Disease Clinical Research Consortium (RDCRC)

描述（由申请人提供）：我们建议继续并扩大卟啉症联盟（PC）的临床研究和培训计划，该联盟是罕见疾病临床研究网络（RDCRN）目前资助的联盟，专注于血红素生物合成的先天性错误，卟啉症。PC汇集了六个区域中心的资深卟啉症专家的互补优势；美国卟啉症基金会（APF），美国唯一的卟啉症患者倡导和支持团体；生物制药公司对改善诊断和/或开发针对这些不同疾病的新疗法感兴趣。首席研究员和行政主任将分别是西奈山伊坎医学院（MSSM）的Robert J. Desnick博士和加尔维斯顿德克萨斯大学医学分部的Karl E. Anderson博士。其他四位联盟董事是加州大学旧金山分校（UCSF）的Montgomery Bissell博士；Joseph R. Bloomer医学博士，阿拉巴马大学伯明翰分校（UAB）；赫伯特L.邦科夫斯基，医学博士，卡罗来纳医疗保健系统（CHS）；约翰·菲利普斯博士，犹他大学（UoU）。这些卟啉症专家组成了一个互动和跨学科的转化和临床研究团队，他们有活跃的基础和临床卟啉症研究项目，在培训年轻研究人员方面有着良好的记录，以及国际公认的临床专业知识。在过去的四年里，他们作为一个有效的团队工作，以完成PC的原始目标，这些目标记录在每个项目的进度报告中。PC在不到三年的时间里招募了450多名患者进行纵向研究（LS），以记录每种卟啉症的自然历史，并启动了其他六项临床研究或试验。

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.