Creating action with information: The Rare Disease Community Cary O. Harding, MD Department of Molecular & Medical Genetics.
Download ReportTranscript Creating action with information: The Rare Disease Community Cary O. Harding, MD Department of Molecular & Medical Genetics.
Creating action with information: The Rare Disease Community Cary O. Harding, MD Department of Molecular & Medical Genetics Disclosures • BioMarin Corporation – Funds for participation in clinical trials • Sapropterin dihydrochloride • rAvPAL-PEG • National PKU Alliance – Funds for PKU gene therapy research Take home messages • The future of PKU research and treatment is very promising. • The barriers to progress are shared by many rare disorders. • Collaborative efforts are critical to maintaining progress. • Patient advocacy groups (eg. NPKUA) have immense impact. TEAMWORK • http://photos.presstelegram.com/2012/07/ph otos-cycling-at-the-london-2012-olympicsjuly-28/ - 6 Outline • Future treatments • Current therapy • Legislative and regulatory issues Future therapy • • • • • rAvPAL-PEG Novel large neutral amino acid therapies Probiotic therapy Hepatocyte transplantation Gene therapy Collaboration is essential! • rAvPAL-PEG – Proof of concept in academic center • McGill University – Further refinement in private foundation lab • Scripps Institute – Preclinical validation in an academic center with pharmaceutical company support • University of Florida – Clinical trials in multiple centers • BioMarin rAvPAL-PEG Phase III • • • • More clinical sites Proof of efficacy Investigate self-administration Evaluate side effects – Skin rashes – Joint swelling • Monitor for adverse events Timeline and funding • • • • First published report – 1999 Phase 3 study – 2013 FDA approval - ?2016 Funding – Government grant – Private foundation money – Pharmaceutical company Gene therapy • Preclinical studies – – – – – – Develop preclinical vector Proof of concept Refine vector Investigational new drug application Production of vector in GMP facility Large scale pharmacologic studies • First in human Phase 1 trial Acknowledgements • Grompe Lab - OHSU – – – – Markus Grompe Nick Morcinek Zhongya Wang Laura Roy • Koeberl lab – Duke – Dwight Koeberl – Andy Bird • Thöny lab – Zurich – Beat Thöny – Hiu Man Viecelli – Alex Rebuffat • Harding lab – OHSU – – – – – – – Shelley Winn Katie Cobb Kevin Watanabe-Smith Lindsey Stetson Baoyu Lin Gloria Baca Kelly Hamman • Funding – NPKUA – NIH Status of current therapy • ? Nutritional adequacy of current dietary therapy – Intact protein vs. free amino acids – Micronutrients – Bone effects • Neuropsychologic outcomes • Pathophysiology of PKU Needed investigations • Animal models – How does Phe affect the brain? – What dietary variables affect physical outcome? • Human investigations – Neuropsychologic and imaging studies – Effects of pharmacologic therapy – Long term follow up Recent NIH/FDA efforts • National Center for Advancing Translational Studies (NCATS) – Office of Rare Diseases Research • FDA Office of Orphan Products Development • Meetings in 2011 and 2012 – Further research on medical foods – Research needs specifically for PKU Rare Disorders Consortia • NIH funded with additional philanthropy • Multisite collaborative clinical research – Longitudinal natural history studies – Prospective research studies • Multiple collaborators – – – – Academic centers NIH Patient advocacy groups Pharmaceutical companies Urea Cycle Disorders Consortium • 16 centers – Two in Europe • Longitudinal study – Effectiveness of current therapy – Long term outcomes • Liver disease • Liver tumors • Novel pharmaceutical therapies • NUCDF intimately involved Newborn Screening Translational Research Network • National database • Long term outcome of all disorders detected by newborn screening Legislative efforts • Uniform availability and funding for medical foods – Some states have legislative mandates • Medical Foods Equity Act • Insurance exchanges under Obamacare – Defining minimal benefit package for participating insurance plans Conclusions • The future of PKU treatment and research is promising! • Collaboration essential – – – – – Clinical centers Government agencies Private philanthropic foundations Pharmaceutical companies Patient advocacy organizations The critical catalyst? YOU! NPKUA