Neuropsychopharmacological potential of the bile acid analogon NorUDCA
Prof. Michael Trauner, Medical University of Vienna; Dr Johannes Griessner, Medical University of Vienna; Dr Daniel Steinacher, Medical University of Vienna; Dr Wulf Haubensak, Research Institute of Molecular Pathology (IMP)
Medical University of Vienna
Today, anxiety, depression and obesity pose significant medical problems in present western societies. The high levels of comorbidity of anxiety, depression and obesity together with the high prevalence of each disorder by itself highlight the need for a better understanding of these conditions and how they interact with each other. Accordingly, there is a need for medical intervention in behavioral disorders, in particular in anxiety disorders and in depressions.
Bile acids (BAs) are well known to be essential players in dietary fat absorption. NorUDCA is a synthetic BA analogue that drastically alters the makeup of the endogenous bile acid pool, leading to reduced fat absorption from the gut and dramatically changing the bile acid pool. To evaluate the potential of targeting a putative shared underlying disease mechanism, we tested the effect of chronic NorUrsodeoxycholic acid (NorUDCA) on anxiety and depression-like behavior in mice.
The effect of chronic NorUDCA treatment on high fat diet (HFD)-induced anxiety and a depression-like behavior in mice shows for the first time an effect of a bile acid derivative on the brain to control HFD associated stress, anxiety and depression as well as ameliorating HFD induced- fatty liver disease in mice, deepening our understanding of the shared pathophysiology and treatment of these conditions.
- Shows for the first time a surprising effect of bile acid action on the brain to control HFD-associated stress, anxiety and depression in mice.
- Suggests a novel class of anxiolytics.
- Provides greater insights in the pathophysiology and treatment of the comorbidity anxiety, depression and obesity.
substance has regulatory approval for first medical use
PCT filed Dec 2020
Fuchs, C. D., Traussnigg, S. A. & Trauner, M. Nuclear Receptor Modulation for the Treatment of Nonalcoholic Fatty Liver Disease. Semin Liver Dis 36, 69-86, doi:10.1055/s-0036-1571296 (2016).
Foster, J. A., Rinaman, L. & Cryan, J. F. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiology of stress 7, 124-136, doi:10.1016/j.ynstr.2017.03.001 (2017).
Dixon, J. B., Dixon, M. E. & O'Brien, P. E. Depression in association with severe obesity: changes with weight loss. Arch Intern Med 163, 2058-2065, doi:10.1001/archinte.163.17.2058 (2003)
Gariepy, G., Nitka, D. & Schmitz, N. The association between obesity and anxiety disorders in the population: a systematic review and meta-analysis. Int J Obes (Lond) 34, 407-419, doi:10.1038/ijo.2009.252 (2010).