Description du projet
Une nouvelle approche de la thérapie génique pour traiter le lymphœdème
Le lymphœdème est une maladie invalidante, où des liquides s’accumulent dans un tissu de manière localisée en raison d’un système lymphatique compromis. Il s’agit d’une maladie incurable qui affecte des millions de personnes dans le monde et est le plus souvent la conséquence d’un traitement contre le cancer. L’objectif principal du projet TheraLymph, financé par l’UE, est de développer un traitement pour améliorer cette maladie en utilisant une approche de thérapie génique non intégrative. Le programme de recherche translationnelle du consortium du projet rassemble des scientifiques et des médecins de cinq pays européens et sera axé sur les patients qui ont développé un lymphœdème après un cancer du sein. La recherche déterminera les facteurs de risque de lymphœdème et les principaux acteurs moléculaires impliqués dans la dysfonction lymphatique. L’objectif du projet consiste à valider la meilleure combinaison de molécules pour la thérapie génique et à achever les essais cliniques de phase I/II à l’hôpital affilié.
Objectif
Lymphedema is a disabling condition induced by the accumulation of fluid and fat in the arm or in the leg. It is an untreatable disease that affects 4 millions people in Europe and more than 120 millions people worldwide. It is handicapping, painful and impacts substantially the quality of life. In western countries, lymphedema is generally a consequence of cancer treatments i.e. ten to fifteen percent of women will develop lymphedema after breast cancer. The main objective of Theralymph will be to establish a non-integrative gene therapy for this unmet medical need.
The theralymph translational research program brings together bench scientists from 5 European countries and physicians from the hosted Rangueil hospital in which the PI institute is located to perform a Phase I/II trial focusing on women who developed lymphedema after breast cancer.
Based on decades of disappointing results of monotherapy-gene delivery in cardiovascular diseases, our approach will be based on multiple gene therapy targeting both superficial lymphatic endothelium and deeper lymphatic collectors. We will identify molecules that possess a synergistic effect with the established lymphangiogenic factor VEGFC.
Theralymph project will determine risk factors for lymphedema and cartography the lymphatic network in the pathology. It will decipher whether lymphatic intrinsic molecules or microenvironmental peptides or lipids are modified in the lymphedematous arm to promote the lymphatic dysfunction. Theralymph will validate the best molecule combination that restores the lymphatic drainage in in preclinical lymphedema models before human study.
The Phase I/II gene therapy clinical trial will be performed in the vascular medicine department of Toulouse’s hospital, where the PI laboratory is located. This trial will use an innovative technology based on recently developed non-integrative lentiflash lentiviral vectors that allow a transient and highly efficient in vivo gene delivery.
Champ scientifique
- medical and health sciencesclinical medicineangiologyvascular diseases
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesclinical medicineoncologybreast cancer
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- medical and health sciencesbasic medicinepathology
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Régime de financement
RIA - Research and Innovation actionCoordinateur
75654 Paris
France