Description du projet
Traiter la maladie aiguë du greffon contre l’hôte à l’aide de cellules stromales mésenchymateuses
Les thérapies régénératives basées sur les cellules souches présentent un fort potentiel pour le traitement de divers troubles. La régénération repose sur des cellules souches spécifiques à un tissu ou progénitrices. Les cellules stromales mésenchymateuses (CSM) ont la capacité de former directement des tissus osseux ou cartilagineux. En outre, la réparation endogène indirecte via les propriétés anti-inflammatoires des CSM joue un rôle important dans le traitement de la maladie du greffon contre l’hôte (MGCH). Le projet RETHRIM, financé par l’UE, entend réaliser le premier essai randomisé de phase III contrôlé par placebo pour une thérapie à base de CSM dans le traitement de la MGCH viscérale résistante aux stéroïdes. Le consortium souhaite enrôler 150 patients dans le cadre de l’essai d’analyse des CSM à l’aide de marqueurs moléculaires et fonctionnels pour la prévision de la réponse thérapeutique.
Objectif
Stem cell regenerative therapies hold great promise for patients suffering from a variety of disorders that are associated with tissue or organ injury. Regeneration relies on tissue or organ-specific stem and progenitor cells, but can also aim at promoting the endogenous repair capacity of the body.
Mesenchymal stromal cells (MSC) are undergoing clinical testing in a variety of clinical conditions aiming at repair through direct or indirect mechanisms. Their ability to form bone or cartilage is used to directly repair these tissues. In other conditions their regenerative effects are based on endogenous repair through their anti-inflammatory properties. The latter mechanism is important in the treatment of acute Graft-versus-Host Disease (GvHD). We have been involved in the clinical development from the beginning and we have shown the therapeutic potential. However, no results of controlled randomized phase 3 studies have been published to date, thereby hampering safety and efficacy assessment.
Within our consortium we have developed an academic infrastructure for the harmonized production of MSC. In the RETHRIM proposal this will be combined with our clinical expertise to conduct the first Europe-wide placebo controlled randomized phase III trial using MSC regenerative therapy for the treatment of steroid-resistant visceral GvHD. Central to the RETHRIM project is the clinical trial for which 150 patients will be recruited. All MSC products will be extensively analysed using molecular and functional markers, in order to develop a potency signature for the product and for the prediction of response. We also intend to collect data from additional quality of life, health technology assessment and ethical studies. We will apply for an Orphan Drug Designation in Europe and this may serve as a stepping-stone for the further commercialization of the MSC product, once a positive outcome has been obtained.
Champ scientifique
- social sciencessociologydemographymortality
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesclinical medicineemergency medicinegraft versus host disease
- medical and health sciencesclinical medicinetransplantation
Programme(s)
Régime de financement
RIA - Research and Innovation actionCoordinateur
2333 ZA Leiden
Pays-Bas