PSC Partners Seeking A Cure 2019 Conference PSC
- Slides: 33
PSC Partners Seeking A Cure 2019 Conference PSC Partners Sponsored Research David N. Assis, MD Assistant Professor of Medicine Yale University School of Medicine June 22, 2019
Disclosures • Site sub-investigator for the following autoimmune liver disease trial sponsors: – TARGET-PBC, Genkyotex, High. Tide, Cymabay, Novartis.
PSC Partners Research Awards • Overall goals: support research addressing important, novel basic or clinical questions related to PSC. • 2009: First set of research grants awarded • Over $3, 191, 666 have been allocated to promising PSC research • Strong, ongoing relationship with the research and clinical PSC community around the world
PSC Partners Research Awards • An impressive track record of funding meaningful and timely research projects in PSC in the first 10 years…
PSC Partners Research Awards • Examining the Disease Impact of Genetic Variation in Logical Candidate Genes for PSC: a PROGRESS Study • Konstantinos N. Lazaridis, M. D. , Mayo Clinic
PSC Partners Research Awards • More than 1, 500 PSC patients enrolled • Cutting-edge genetic and genetic-environmental studies Ji et al. Nat Genet. 2017 Feb; 49(2): 269 -273.
PSC Partners Research Awards • A Pilot study of Vancomycin or Metronidazole in patients with Primary Sclerosing Cholangitis. • Keith D. Lindor, M. D. , Mayo Clinic
• ss Tabibian et al. Aliment Pharmacol Ther. 2013 Mar; 37(6): 604 -12.
PSC Partners Research Awards • Potential Role of Cholangiocyte Senescence in PSC. • Nicholas F. La. Russo, M. D. , Mayo Clinic
Tabibian et al. 2014 Jun; 59(6): 2263 -75.
PSC Partners Research Awards • Bile acid-regulation of mast cells in models of primary sclerosing cholangitis and cholangiocarcinoma. • Heather Francis, Ph. D. , Texas A&M Health Science Center
Kennedy et al. Hepatology 2018 (in press)
PSC Partners Research Awards • Distinguishing primary sclerosing cholangitis from Ig. G 4 associated cholangitis: Specific Ig. G 4 class-switched B-cells as diagnostic tool. • Ulrich Beuers, M. D. , Academic Medical Center, University of Amsterdam, The Netherlands.
Hubers et al. Gut 2018 Apr; 67(4): 728 -735.
PSC Partners Research Awards • Intrahepatic bile duct tissue engineering utilizing liver matrix and 3 D bioprinting. • Ramille Shah, Ph. D. , Northwestern University
Lewis et al. Sci Rep 2018 Aug 15; 8(1): 12220.
PSC Partners Research Awards • Fecal microbiota transplantation for the treatment of primary sclerosing cholangitis. • Jessica Allegretti, M. D. , M. P. H. , Brigham and Women’s Hospital
• Fecal Transplantation for PSC • • • Pilot Study (N=10) 30% had an ALP reduction ≥ 50% Abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (p= 0. 02). Allegretti et al. Am J Gastroenterol [epub ahead of print].
PSC Partners Research Awards • A Multicenter Collaboration to Study PSC in Children. • Mark Deneau, M. D. , M. S. , University of Utah
Deneau et al. Hepatology 2017. Deneau et al. Hepatol Commun. 2018 Sep 25; 2(11): 1369 -1378.
PSC Partners Research Awards • PSCATOR – Atorvastatin for the treatment of Primary Sclerosing Cholangitis (PSC) – A randomized controlled study. • Annika Bergquist, M. D. , Karolinska University Hospital, Sweden
PSC Partners Research Awards • Retrospective prescription database study in Sweden • PSC on Statins (N=404) vs. not on Statins (N=2510) • Lower all-cause mortality OR 0. 68 (0. 54 -0. 88) • Lower liver-mortality and transplantation OR 0. 50 (0. 28 -0. 66) • Lower adverse liver events OR 0. 53 (0. 36 -0. 80) • 2019: prospective, randomized placebo-controlled study in Sweden. Stokkeland K et al. Clin Gastroenterol Hepatol 2019 (in press).
PSC Partners Research Awards • Characterization of clinical and immunologic phenotypes of patients with recurrent PSC after liver transplantation: An international network study. • Aliya Gulamhusein, M. D. , M. P. H. , F. R. C. P. C. , University of Toronto • Aims: • Comprehensively characterize (phenotype) a prospective cohort of patients with PSC post liver transplant and use newly emergent mass cytometry technology to understand clinical, serologic, microbiological, and immunologic changes associated with development of r. PSC. • Establish an international network among liver transplant centers worldwide to characterize clinical risk factors associated with r. PSC.
PSC Partners Research Awards • An investigation of biliary-immune interactions and candidate drug-screening using novel bile-derived organoid technology. • David N. Assis, M. D. , Yale School of Medicine
PSC Partners Research Awards Soroka et al. Hepatology 2019 (in press).
2019 Awards! • 4 Projects Awarded by PSC Partners
2019 Awards • Metabolomic-based prediction of prognosis in patients with Primary Sclerosing Cholangitis and early diagnosis of Cholangiocarcinoma: new non-invasive strategy. • Jesus Banales, Ph. D. , Biodonostia Institute, Spain Aim: • Test the hypothesis that patients with PSC have specific serum metabolic profiles that can be used for early diagnosis, to predict prognosis, recurrence after liver transplantation, and cholangiocarcinoma.
2019 Awards • PI: Jesus Banales, Ph. D. Banales et al. Hepatology 2019 (in press).
2019 Awards • Single-cell RNA sequencing of lymphocyte subsets and cholangiocytes in non-endstage PSC patients. • Cyriel Ponsioen, M. D. Ph. D. , Academic Medical Center, Amsterdam Aim: • Characterize immune cell subsets and cholangiocytes in active inflammation acquired from cholangioscopy in the central/extrahepatic bile ducts through surface markers and in-depth transcriptomic analysis.
2019 Awards • Pathways of Injury and Repair of the Extrahepatic Biliary Tree in PSC. • Orith Waisbourd-Zinman, M. D. , Schneider Children’s Medical Center of Israel Aim: Investigate the role of decrease in glutathione (GSH) in bile duct injury and repair, based on the suggestion that decrease in GSH can cause cholangiocyte damage, while increase in GSH can improve duct damage.
2019 Awards • Genome Wide Association Study (GWAS) in Biliary Tract Cancer (BTC). • Lewis Roberts, M. B. , Ch. B. , Ph. D. , Mayo Clinic Hypothesis: Unique host genetic factors can predict cholangiocarcinoma risk in non-PSC cases, whereas other markers may predict CCA development in patients with PSC and clinical outcomes in CCA. Aim: Verify novel loci and genetic factors that influence susceptibility to CCA in patients with and without PSC.
PSC Partners Research Awards • Research support is extremely important for generating real progress in the study and care for patients with PSC • PSC Partners continues to have a very high impact in this field by promoting the most promising ideas in PSC • The benefits of this funding are profound after the first 10 years of awards.
PSC Partners Research Awards • Research support is extremely important for generating real progress in the study and care for patients with PSC • PSC Partners continues to have a very high impact in this field by promoting the most promising ideas in PSC • The benefits of this funding are profound after the first 10 years of awards. THANK YOU!
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