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GCG-T3 Dyslipidemia SIGNED

Validation and Molecular Characterization of Novel Glucagon-Thyroid Hormone Conjugates for the Efficient Management of Dyslipidemia and Fatty Liver Disease

Total Cost €

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EC-Contrib. €

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Partnership

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Project "GCG-T3 Dyslipidemia" data sheet

The following table provides information about the project.

Coordinator
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH 

Organization address
address: INGOLSTADTER LANDSTRASSE 1
city: NEUHERBERG
postcode: 85764
website: www.helmholtz-muenchen.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website https://www.2minutemedicine.com/targeted-thyroid-hormone-delivery-reduces-off-target-effects-preclinical/
 Total cost 171˙460 €
 EC max contribution 171˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-04-01   to  2018-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH DE (NEUHERBERG) coordinator 171˙460.00

Map

 Project objective

Cardiovascular disease (CVD) is a leading cause of death worldwide. Compelling evidence indicates that dyslipidemia represent a key risk factor for CVD. Among approved lipid-lowering agents, statins are the most effective therapy for CVD. However, a substantial portion of high-risk patients treated with statins fail to achieve target cholesterol levels required for preventing CVD. Thus, sufficiently efficacious and safe alternatives are urgently required. In addition, non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease, contributes to dyslipidemia and accelerates CVD progression. However, limited therapeutic options are available for the treatment of NAFLD. Interestingly, the host group has developed a novel strategy of peptide-nuclear hormone conjugates that allows for peptide-mediated selective tissue targeting of nuclear hormones, which enables for synergistic benefits in target tissues while avoiding adverse effects in off-target tissues. The current project, aims to develop a novel poly-pharmaceutical therapy for the treatment of dyslipidemia and NAFLD by combining two key hormones in the control of lipid metabolism: glucagon and thyroid hormone (T3). To this end, the host group synthesized a series of glucagon-T3 conjugates to allow liver specific delivery of T3 aiming to reduce serum lipid levels and reverse hepatic steatosis, without causing adverse cardiovascular effects. During the implementation of this project the applicant will assess the in vivo efficacy of the conjugates in a series of rodent models of the metabolic syndrome, hypercholesterolemia and NAFLD. In addition, the applicant will characterize the molecular mechanisms by which the conjugates induce their metabolic benefits, while carefully assessing the potential adverse effects that the conjugates may cause in off-target tissues. This project may ultimately facilitate the discovery and the development of a novel and more effective therapy against dyslipidemia and NAFLD.

 Publications

year authors and title journal last update
List of publications.
2016 Brian Finan, Christoffer Clemmensen, Zhimeng Zhu, Kerstin Stemmer, Karine Gauthier, Luisa Müller, Meri De Angelis, Kristin Moreth, Frauke Neff, Diego Perez-Tilve, Katrin Fischer, Dominik Lutter, Miguel A. Sánchez-Garrido, Peng Liu, Jan Tuckermann, Mohsen Malehmir, Marc E. Healy, Achim Weber, Mathias Heikenwalder, Martin Jastroch, Maximilian Kleinert, Sigrid Jall, Sara Brandt, Frédéric Flamant, Karl-Werner Schramm, Heike Biebermann, Yvonne Döring, Christian Weber, Kirk M. Habegger, Michaela Keuper, Vasily Gelfanov, Fa Liu, Josef Köhrle, Jan Rozman, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabě de Angelis, Susanna M. Hofmann, Bin Yang, Matthias H. Tschöp, Richard DiMarchi, Timo D. Müller
Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease
published pages: 843-857.e14, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.09.014
Cell 167/3 2019-06-13

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