Description du projet
Des systèmes modèles innovants pour étudier les maladies osseuses
Les traitements médicamenteux conventionnels qui ciblent la perte osseuse évitent les fractures ostéoporotiques chez seulement 50 % des personnes atteintes, et la charge économique à l’échelle mondiale de ces traitements devrait atteindre les 132 milliards de dollars d’ici 2050. Le problème actuel auquel la recherche clinique internationale est confrontée est que nos meilleures connaissances sur la biologie et la physiopathologie des os proviennent de cultures cellulaires en 2D, qui ne parviennent pas à saisir les aspects biomécaniques vitaux des os, ou d’études menées chez des animaux dont la biologie diffère de celle des êtres humains. Le projet MEMETic, financé par l’UE, entend élaborer des modèles ex vivo avancés dans un environnement 3D multicellulaire pour reproduire la fonction mécanobiologique de l’os. Les modèles de MEMETic permettront d’améliorer nos connaissances sur le développement de l’ostéoporose et de fournir une évaluation des nouveaux traitements.
Objectif
Despite immense efforts to develop therapies for osteoporosis, conventional drugs that target bone loss only prevent osteoporotic fractures in 50% of sufferers, and the worldwide economic burden of treatment is projected to reach $132 billion by 2050. Recently our research has (1) identified important tissue-level changes in osteoporotic bone and (2) provided evidence that the biological mechanisms by which the cells normally respond to their mechanical environment are altered. However, no existing therapeutic approach has been developed to account for these. It is timely to build upon our important research findings and significantly advance the state of the art in the field of mechanobiology to understand osteoporosis aetiology and ultimately inform effective therapies.
A particular challenge for the international research field, has been that most current understanding of bone biology and pathophysiology has been derived either using 2D cell culture, which fails to capture vital biomechanical aspects of bone that govern bone biology, or animal studies, whose biology differs from that of humans. So, existing approaches cannot fully capture, or account for both human biological and mechanical factors, and this project seeks to address this challenge.
The global objective of the MEMETic project is to provide a paradigm change for studies of bone disease and therapeutics by consolidating, and significantly advancing, our novel approaches to develop advanced ex vivo models that recreate in vivo biomechanical cues in a living and multicellular 3D environment to replicate the mechanobiological function of bone. The MEMETic models will be applied to advance understanding of osteoporosis and a new osteoporosis therapy (sclerostin antibody). A unique multidisciplinary approach, combining cell and molecular biology with biomechanical and mechanobiological techniques, will enable these important advances, and consolidate a world leading mechanobiology research program.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
H91 Galway
Irlande