ACHIEVE: Development of an oral ACG-based treatment to combat obesity, maintain long-term dieting success and improve metabolic health

Description du projet

Un traitement oral à base de métabolites contre l’obésité avec des résultats à long terme

L’obésité est une épidémie mondiale qui comporte de graves risques pour la santé. Bien que les traitements par GLP-1 puissent favoriser la perte de poids, il n’est pas facile de la maintenir. Des recherches suggèrent que certains métabolites pourraient influencer la prise de poids. Cependant, il n’existe pas de solutions orales efficaces pour le maintien du poids à long terme en complément de ces thérapies. Le projet ACHIEVE, financé par le CER, vise à développer un traitement ou un complément à base de métabolites qui réduise en toute sécurité la prise de poids, maintient la perte de poids à long terme et améliore la fonction métabolique. Il permettra de créer des médicaments et/ou des aliments médicaux à base de métabolites, dont l’efficacité, la sécurité et le mécanisme seront testés sur des souris obèses et maigres, avant de procéder à un premier essai sur des personnes obèses traitées au GLP-1. Il portera également sur la commercialisation.

Objectif

Obesity constitutes an alarming global epidemic, exposing billions of individuals to a multitude of metabolic, infectious, & neoplastic health ramifications. While weight reducing interventions of the GLP-1 family are transforming medical weight reductive therapy, long-term weight loss maintenance remains a daunting unmet challenge, with most medically treated individuals rebounding to obesity. In our project, we will generate a first-of-its kind solution to this global need that will involve oral human utilization of microbiome-modulated weight-regulating interventions. In our ERC-funded project (Fluhr et al., Nature 2021), we discovered that depletion of several microbiome-modulated metabolites drives weight gain in smoking-cessation-induced weight gain. Oral supplementation of several of these molecules has led to a generalizable & significant weight reduction across multiple obesogenic conditions.
Building on these findings, the ERC-PoC will develop a commercial metabolite-based treatment or supplement, that will safely attenuate weight gain, maintain long-term weight reducing impacts, and improve metabolic functions. The project includes four work packages:
(1) Development and production of metabolite-based drugs and/or medical foods (following a rigorous market study in a dual path approach). (2) Testing these molecules for efficacy, mechanism and safety in obese/lean mice. (3) performing a first-in-human trial (using the most efficacious formulation) in obese/GLP-1-treated individuals (4) in parallel, conducting an extensive commercialization effort to translate our findings into a NewCo, based on 1-2 new products. Notably, there is currently no such orally administered long-term solution complementing weight-reducing therapies in maintaining weight over time. As such, our ERC-PoC project will provide a proof-of-concept product/s for prevention & treatment intervention, providing a unique and commercially scalable solution to an important unmet global problem.