PORPHYRIAS CONSORTIUM OVERALL ABSTRACT 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 Coordiantor will be Robert J. Desnick, PhD, MD, Icahn School of Medicine at Mount Sinai (ISMMS) and John D. Phillips, PhD, University of Utah (UoU), respectively. The other four Consortium Directors are Karl E. Anderson, MD, University of Texas Medical Branch, Galveston (UTMB), D. Montgomery Bissell, MD, University of California at San Francisco (UCSF); Brendan McGuire, MD, University of Alabama at Birmingham (UAB); and Herbert L. Bonkovsky, MD, Wake Forest University (WF). 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 nine years, they have worked as an effective team to accomplish the original objectives of the PC as documented in the overall progress report. The PC has recruited over 840 patients in <9 years to the Longitudinal Study (LS) to document the natural history of each porphyria, and initiated nine other clinical studies or trials, and several pilot/demonstration projects. We will continue to enroll patients into the LS. In addition, we will continue training the next generation of porphyria experts, supported by grants donated by patients and industry. These will also support the expansion of our Satellite Sites which participate in the LS. New studies will focus on phase 1 clincial trials of repurposed drugs as treatments for the erythopoietic porphryias, identification of new causative genes for the Acute Hepatic Porphyria and Erythropoietic Protoporphyria phenotypes, identification of modifier genes for Acute Intermittent Porphyria, establishing an international diagnostic collaborative to better diagnose porphyria patients, and a pilot clinical trial assessing Harvoni as a sole treatment for porphyria cutanea tarda. These studies should lead to more effective management and treatment of these diseases. It is the intention of the PC to continue as a dedicated Consortium after year 15 of RDCRN funding. We expect that this 5 year renewal will generate sufficient new diagnostic and treatment information to allow us to apply for additional grants to maintain the infrastructure of the PC and support innovative research.
PORPHYRIAS CONSORTIUM OVERALL NARRATIVE The hepatic and erythropoietic porphyrias are rare inborn errors of heme biosynthesis that are unrecognized or misdiagnosed, and in need of improved and specific therapies. Prior to our Consortium, their rarity limited characterization of their clinical manifestations, natural histories, and genotype/phenotype correlations. We have made significant progress in characterizing these diseases, as this Consortium brings together senior porphyria experts, the American Porphyria Foundation, and industry to address these limitations, and we will continue to conduct novel clinical trials and studies, and train porphyria clinicians and researchers. 1
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