Reversing Hypertriglyceridemia and Hepatic Steatosis in Dysmetabolic NHPs with a Controlled-Release Mitochondrial Protonophore (CRMP)
Presenter: Dr. Leigh Goedeke, Postdoctoral Fellow, Yale School of Medicine
NAFLD is a major predisposing factor in the pathogenesis of hepatic insulin resistance, NASH, and T2D. New therapies are required to reverse NAFLD, insulin resistance, and diabetes - current weight loss options are effective but difficult to sustain.
The Shulman Lab at Yale University has developed a controlled-release mitochondrial protonophore (CRMP) for the treatment of NAFLD/NASH and T2D. CRMP is functionally liver-targeted and promotes hepatic triglyceride oxidation through a subtle, sustained increase in hepatic mitochondrial inefficiency. CRMP safely reverses hypertriglyceridemia, fatty liver, and hepatic inflammation/fibrosis in diet-induced rodent models of obesity, and there is now a critical need to assess CRMP safety and efficacy in models more relevant to human disease.
In this webinar, Dr. Leigh Goedeke reviews spontaneous nonhuman primate (NHP) models of NAFLD and metabolic syndrome as a more clinically-relevant preclinical study platform. She also presents data on the impact of CRMP treatment on hepatic mitochondrial oxidation and the reversal of hypertriglyceridemia, NAFLD, and insulin resistance in these models.
Watch this Webinar to:
- Learn more about spontaneous NHP models of NAFLD and metabolic syndrome as a human disease-relevant preclinical platform
- Explore important proof-of-concept NHP study data to support the development of novel liver-targeted mitochondrial uncouplers for the treatment of NAFLD/NASH and T2D in humans
- Learn how liver-targeted mitochondrial uncoupling improves dyslipidemia and reduces hepatic triglyceride content in obese NHPs
- Explore how CRMP promotes oxidation of hepatic triglycerides by promoting a subtle sustained increase in hepatic mitochondrial inefficiency
- Observe data showing that acute CRMP treatment significantly increases rates of hepatic mitochondrial fat oxidation, and reduces hepatic and plasma triglycerides, as well as endogenous glucose production
- Discover Positional Isotopomer NMR Tracer Analysis (PINTA), a non-invasive tracer method to model hepatic mitochondrial metabolism in vivo
Who Should Watch:
- Preclinical scientists interested in learning more about CRMP and PINTA assays
- Drug developers working on therapeutics for NAFLD/NASH, dyslipidemia, or type 2 diabetes
- Researchers evaluating large animal models or new techniques for NAFLD/NASH preclinical studies
About The Presenter:
Dr. Leigh Goedeke is a Postdoctoral Fellow at Yale School of Medicine, in the laboratory of Dr. Gerald Shulman. With extensive experience in multiple metabolic disease indications, Dr. Goedeke specializes in the interplay between hepatic steatosis, insulin resistance, type 2 diabetes, and cardiovascular disease. As part of the Shulman lab, Dr. Goedeke uses stable isotope tracer methods to understand how alterations in metabolic fluxes contribute to the pathogenesis of insulin resistance and is investigating the therapeutic potential of liver-targeted mitochondrial uncoupling agents to reverse metabolic syndrome.
Dr. Goedeke received her Ph.D. in Biomedical Sciences from New York University School of Medicine where she identified and characterized novel genes and miRNAs involved in lipid metabolism using functional genomic screens. She has authored over 30 publications, and holds a patent in a specialized oligonucleotide as a therapeutic tool for treating dyslipidemias and cardiovascular diseases.