Organ-crosstalk and Biomarker Discovery in NASH/Fibrosis


2nd Mar 2021



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Organ-crosstalk and Biomarker Discovery in NASH/Fibrosis

Using Translational Preclinical Models

Date: 2nd March 2021 (Tuesday)
Start Time: New York 09:00 | London 14:00 | Paris 15:00 | Singapore 22:00 | Tokyo 23:00 | Sydney 01:00 (3 Mar)
Duration: 120 minutes
Event Structure: 5-minute introduction + 35-minute TNO presentation + 15-minute Q&A + 65-minute panel discussion
Registration fee: Complimentary access

In this webinar TNO’s translational mouse models for preclinical research of NAFLD will be discussed. The translational characteristics of the models will be explained using different approaches to translate mechanisms to human situations. The contribution of other organs to NAFLD/NASH will be addressed with particular emphasis on dysfunctional adipose tissue and gut permeability. An overview of different compound classes employed in aforementioned models will be provided and rationales for combination therapies discussed. It will be shown that TNO’s preclinical models are also suitable to assess atherosclerosis as secondary endpoint, which is of translational relevance because CVD is a major cause of death in NAFLD patients. Finally, it will be demonstrated that TNO’s translational models allow identification of new biomarkers that inform on onset and progression of liver fibrosis and reflect fibrosis staging in human cohorts.

The panel discussion focuses on the differences between human physiology and preclinical models and how this determines the choice of an appropriate model. The role of metabolic homeostasis, inflammation and organ cross talk within NAFLD/NASH will be discussed and how this could affect intervention strategies. Finally we will debate which end point parameters improve assessment of pathology and the role of biomarker signatures therein.

Presentations will be given by:

Dr Kanita Salic has a background in molecular biology and joined TNO in the year of 2012. Her work includes a.o. studying metabolic and inflammatory-related complications such as NAFLD, obesity and cardiovascular disease, using translational models. As a study director, she is involved in multiple projects including both pharma and nutritional industries and works in different consortia with emphasis on designing strategies that could attenuate the burden of metabolic-inflammatory complications.

Dr. rer. nat. Robert Kleemann is a biochemist with expertise in the field of ‘Nutrition and Metabolism’. His research involves human and preclinical studies and centers around the role of metabolic inflammation as a driver of metabolic and cardiovascular pathologies. He is associated with the Leiden University Medical Center (Vascular Surgery; Associate Professor) and Wageningen University (Physiology and Nutrition). His interests include novel pharmacological and nutrition treatments that improve systemic health and restore metabolic balance to resolve inflammation, the development of translational experimental models and the application of omics technologies to unravel disease mechanisms. The latter is of particular interest for the identification of functional biomarkers, patient stratification and translation of findings between species. As a Principal Scientist at TNO, he established a large international consortia involving multiple scientific disciplines and a broad spectrum of academic and private partners. Example of such private public partnerships of TNO are ‘ProLiver’ (new approaches for NAFLD/NASH and vascular health); ‘Muscle Health’ (gender differences in metabolic control critical for aging and frailty) and ‘GLoBAL – Body-Brain-Interactions’ (organ crosstalk and development of human and preclinical platforms to study metabolism and inflammation)

Dr Arianne van Koppen has a background in chronic kidney disease and joined TNO in 2017. She is a study director within the Metabolic Health Research department and project leader of multiple projects including both fee for service and public private partnerships. One of these PPPs is on the identification and verification of human biomarkers for early detection of NASH-induced fibrosis, which has resulted in a molecular signature that predicts the onset of fibrosis in NASH. She is also project leader of a PPP focusing on the development of a translational mouse model of diabetic nephropathy.

Dr Erhardtsen has more than 25 years of experience in the pharmaceutical industry within the fields of liver disease, cancer, hemophilia, women’s health care and diabetes. Recently on behalf of LITMUS she was responsible for FDA approval of 2 LOIs within NASH in relation to Biomarker Qualification, (this work has received support from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking (LITMUS grant no. 777377). Dr Erhardtsen has been accountable for more than 50 clinical protocols at various clinical development levels, she spearheaded FDA approvals of several recombinant products and devices. Dr Erhardtsen has worked as Regulatory Vice President with Novo Nordisk in the US, and as Global Regulatory Senior Director with Baxter in Austria, and Bayer in Germany. Dr Erhardtsen is known for her in depth expertise in dealing with FDA with whom she has been responsible for approvals and opening >25 INDs. She has written book chapters in Schiff’s Diseases of the Liver, 9th Edition 2002, Lippincott Williams & Wilkins, New York, NY, Directory of Therapeutic Enzymes, 2005. CRC Press, Taylor & Francis Group, Boca Raton FL, In Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine, Ganten D, Ruckpaul K (Eds.) Springer Verlag GmbH 2006, and most recently The Regulatory path for Companion/Complementary Biomarkers; Page 373-384, Biochemistry of Collagens, Laminins and Elastin 2nd edition, Academic press 2019.

Jim Trevaskis currently heads the Fibrosis Biology research group at Gilead, leading internal initiatives and external collaborations in target discovery and drug development in the areas of NASH, PSC, fibrotic lung diseases and diabetic kidney disease. He has extensive prior experience as project team leader and pharmacologist in diabetes and obesity research programs at AstraZeneca/MedImmune, Novartis and Amylin Pharmaceuticals. Jim is expert in the application of combination strategies (co-administration of single agents, peptide-hybrids, dual agonists, etc.) for metabolic diseases such as obesity and NASH.

Dr. Amalia Gastaldelli is the Research Director of the Cardiometabolic Risk UNIT at the Institute of Clinical Physiology of CNR in Pisa Italy. Her main research interest is on pathophysiological mechanisms leading to metabolic diseases such as non alcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes. These include alterations in glucose and lipid metabolism, insulin resistance and ectopic fat accumulation collaborating with many institutions in Europe and the United States. She is currently the chair of the EASD NAFLD Study Group, which provides a joint forum for diabetologists and hepatologists to explore the diagnosis, pathogenesis and treatment of NAFLD and NASH, and the chair of the EASD EGIR Study Group which focuses on insulin action and secretion. She was part of the EASL-EASD-EASO committee for the writing of the “Clinical Practice Guidelines for the management of NAFLD” (2016).

Henning Grønbækis a Professor in Hepatology with a key interest in metabolic associated fatty liver disease and conducted experimental and clinical studies related to inflammation and fibrosis including interventions. Research has focused on macrophages and macrophage activation markers in MALFD and other other chronic inflammatory liver diseases. In addition co-author on national guidelines and international position papers in MAFLD.

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