Project: Exosomes as innovative Nanomedicine Approaches to reverse obesity and its MEtabolic and Psychotic complications with specific targeting of the hypothalamus
| Acronym | ENAMEP (Reference Number: EURONANOMED2019-050) |
| Duration | 01/01/2020 - 31/12/2022 |
| Project Topic | The network aims to develop a “nanobiomedicine” approach to harness the biology of nanoscaled exosomes as an innovative approach to assess suitable tools for specific targeting of the hypothalamic areas modulating energy balance. We aim to deliver DNA in specific neuronal hypothalamic populations to open a new avenue in pharmacological treatment of metabolic complications. Our hypothesis is based on our expertise of hypothalamic lipid metabolism by increasing brown adipose tissue (BAT) thermogenesis. This can be obtained via specific inhibition of the targets AMPK, GRP78 and NLRP3 in the ventromedial nucleus of the hypothalamus by the use of peripherally administered engineered exosomes. The following objectives will be taken: - validation of engineered exosomes driven by SF1 promoter from mouse immature dendritic cells in vitro and in vivo to be delivered specifically in the hypothalamic neuron dominant negative (DN) of AMPK, wild type (WT) of GRP78 and DN of NLRP3 exosomes; - proof of concept in vivo of the effects of exosomes driven by SF1 on energy metabolism in obese models (body weight, glucose and lipid metabolism, BAT thermogenesis); - investigation of the molecular pathways in SF1 neurons mediating the effects of AMPKa-DN, GRP78-WT and NLRP3-DN; - study of the effect of SF1 exosomes on energy metabolism and body weight in rodent models of antipsychotic drug-induced weight gain; - production of human exosomes from freshly monocyte-derived dendritic cells under Good Manufacturing Practice conditions to transfer them to the clinic. This program will establish an innovative exosome-based nanomedicine approach challenging obesity-related diseases. Controlling central regulation of obesity through this approach would spawn the definition of new strategies to monitor efficacy of therapy with minimal side effects. The use of these exosomes is the only way to target specific hypothalamic area by intravenous delivery, making them affordable for therapeutic use. |
| Network | EuroNanoMed III |
| Call | Joint Transnational Call (2019) |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | Université d'Angers | Coordinator | France |
| 2 | Instituto de Investigación Sanitaria, Santiago de Compostela (IDIS) | Partner | Spain |
| 3 | Haukeland University Hospital | Partner | Norway |
| 4 | Institut national de la santé et de la recherche médicale (INSERM) | Partner | France |