Description du projet
Un traitement personnalisé pour la lombalgie
La lombalgie provoquée par la dégénérescence des disques intervertébraux (DIV) est une préoccupation croissante de santé dans notre société. Même si divers biomatériaux et différentes thérapies cellulaires font l’objet d’essais cliniques, il s’avère peu probable qu’une approche «universelle» soit efficace en raison des différents microenvironnements de chaque DIV. Le projet INTEGRATE, financé par l’UE, propose de combiner le criblage in vitro et la modélisation in silico pour concevoir des thérapies cellulaires en fonction du profil individuel des DIV et prédire leur régénération. Le projet développera également des biomatériaux activés par des gènes capables de régénérer la matrice endommagée des DIV et de moduler les processus inflammatoires, ouvrant ainsi de nouvelles voies pour la mise en place de stratégies thérapeutiques peu invasives.
Objectif
Lower back pain is a global epidemiological and socioeconomic problem. Biomaterial and cell-based therapies have been pursued for the treatment of degenerated intervertebral disc (IVD), with a number of clinical trials underway. However, the degenerated intervertebral disc has a distinct environment (e.g. altered oxygen, glucose, acidity, inflammatory cytokine levels) that is unique to an individual (i.e. patient-specific) and will ultimately determine the likelihood and rate at which regeneration can occur. A “one size fits all” approach will lead to the failure to demonstrate efficacy of advanced therapies, as they are not being designed or personalised for individual patients. This proposal envisions a future whereby advanced gene activated cell therapies are personalised (targeting regeneration or modulating inflammation) to treat back pain based on knowing the individuals unique disc microenvironment. This will be achieved through profiling of individual patient disc microenvironmental factors, with in vitro screening and in silico modelling to design cell therapies and predict regeneration outcomes (Aim 1) combined with the development of tailored functionalised gene activated biomaterials (Aim 2), to enhance matrix formation and modulate the inflammatory processes (Aim 3). Gene-based therapy offers several advantages over direct delivery of proteins or small molecules, among them the possibility of sustained efficacy and endogenous synthesis of growth factors or suppression of inflammatory factors and pathways. The platform technology (personalised gene activated biomaterials to regulate regeneration and inflammation) and knowledge (tailoring cell therapies to suit patient-specific microenvironments) generated through this research are beyond the current state-of-the-art and will provide a significant transformative scientific and clinical step change opening new horizons in minimally-invasive therapeutic strategies.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
D02 CX56 DUBLIN 2
Irlande