Rare Organic Acidemias Research (ROAR) Consortium

About This Grant

ABSTRACT – OVERALL Organic acidemias are a group of life-threatening disorders of intermediary amino acid metabolism. Initial signs and symptoms of the disorders include lethargy, poor feeding, seizures, and coma in the neonatal period. Life- threatening metabolic perturbations that occur during acute decompensation events may include metabolic acidosis, hyperammonemia, and hypoglycemia. For nearly 20 years, these disorders have been included on the Recommended Uniform Screening Panel (RUSP) for newborn screening, which has facilitated diagnoses and introduction of therapy. Prompt diagnosis and therapy have increased survival and consequently, uncovered long-term consequences of organic acidemias that include renal failure, cardiomyopathy, feeding and gastrointestinal pathologies, and neurological complications. However, the impact of these long-term complications is unclear, and the options for therapy for this cohort of individuals are limited. The emergence of the initial newborn-screened cohort of individuals with organic acidemias into adulthood highlights the significant unmet need for improved characterization of the natural history of these disorders and for clinical trial readiness as newer therapies are investigated. In response to this unmet need, we propose to establish a Rare Organic Acidemias Research (ROAR) Consortium as part of the Rare Diseases Clinical Research Network (RDCRN). The ROAR Consortium will be a collaborative network with the coordinating site in Houston, TX (Baylor College of Medicine/Texas Children’s Hospital) and consortium sites in Washington, D.C. (Children’s National Medical Center), Pittsburgh, PA (University of Pittsburgh), Minneapolis, MN (University of Minnesota), and Denver, CO (University of Colorado). Two patient advocacy groups, the Organic Acidemias Association (OAA) and Propionic Acidemia Foundation (PAF), will join the ROAR consortium as active members to provide input from the organic acidemia community, including patients and families. In addition, the consortium will collaborate with the intramural program at the National Human Genome Research Institute, which has longstanding clinical research experience in organic acidemias. In the initial cycle, this collaborative research network will work together to advance understanding of the natural history of the disorders and to lay the groundwork for future clinical trials of new therapeutic approaches for these disorders. We will accomplish this goal with the following aims: 1) To perform collaborative, multi-site, clinical and translational research in organic acidemias that will prioritize patient/community concerns, enhance knowledge, improve care, and advance clinical trial readiness, 2) To train and attract a cohort of investigators in organic acidemias research, 3) To serve as a hub for the development of innovative new strategies for managing and treating organic acidemias, and 4) To collaborate with two patient advocacy groups, the RDCRN Data Management and Coordinating Center, and other RDCRN consortia to advance care and educate patients, families, and healthcare providers across a broad spectrum of rare diseases.