Rare Diseases Clinical Research Consortia (RDCRC) for the Rare Diseases Clinical Research Network (RDCRN) (U54 Clinical Trial Optional)

点击翻译按钮获取中文摘要

OVERALL ABSTRACT Urea Cycle Disorders (UCD) comprise a group of rare inborn errors of metabolism that historically have been associated with a rate of mortality and morbidity that once was considered intractably high. The Rare Diseases Clinical Research Consortium in Urea Cycle Disorders (UCDC) has enjoyed success in attenuating and even reversing this lamentable situation. The UCDC focuses on the 8 related disorders that involve deficiencies in one of the 6 enzymes and 2 membrane transporters essential for urea biosynthesis: N-acetylglutamate synthase deficiency; Carbamyl phosphate synthase I deficiency; Ornithine transcarbamylase deficiency; Argininosuccinate synthase deficiency; Argininosuccinatelyase deficiency; Arginase deficiency (Argininemia); Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome; and Citrullinemia type II. Over the past 15 years the Consortium has developed into an international network of 16 academic centers (13 in the U.S., 1 in Canada, and 2 in Europe) that provides state-of-the-art care and conducts innovative clinical research in UCD. In the next grant cycle the UCDC proposes four specific aims: 1) To advance our understanding of the pathophysiology of UCD through collaborative clinical research that includes three projects: a) a longitudinal observational, “natural history” study of affected individuals with an expanded focus on mining the wealth of coded clinical data to uncover new morbidities in UCD; b) a clinical study to understand the consequences of seizure activity and define potential neuroprotective treatment approaches during hyperammonemic crises; and c) an observational study of the development of liver dysfunction and disorder over time in individuals with UCD, including defining biomarkers of hepatic fibrosis. 2) To nurture the development of the next generation of rare disease researchers by training this still- nascent cadre to become expert in the performance of team science clinical investigation of rare genetic disorders, especially UCD. 3) To identify promising new approaches to UCD care by performing pilot/feasibility clinical research projects that will deploy state-of-the-art methodologies and technology to monitor and track patients in the clinic and with deployment of technologies to enable remote observation. 4) To disseminate knowledge and improve the care of UCD by providing ready access to information for all individuals whose efforts will impact outcome, including researchers (both basic and clinical), physicians, and allied healthcare professionals by professional meetings and listservs, our website, podcasts and webinars. Of importance to the Consortium also will be dissemination of information to patients, families, representatives in government and the lay public. The Consortium will execute this informational role through the UCDC’s annual newsletter, public website, presentations at conferences, and publications.