Project description
Treatment of acute graft-versus-host disease using mesenchymal stromal cells
Regenerative therapies based on stem cells hold great potential for the treatment of a variety of disorders. Regeneration relies on tissue-specific or progenitor stem cells. Mesenchymal stromal cells (MSC) have the ability to directly form bone or cartilage tissues. Moreover, indirect endogenous repair via the anti-inflammatory properties of MSCs is important in the treatment of acute graft-versus-host disease (GvHD). The EU-funded RETHRIM project aims to conduct the first placebo-controlled randomised phase III trial for MSC-based therapy in the treatment of steroid-resistant visceral GvHD. The consortium proposes the recruitment of 150 patients for the trial to analyse MSC using molecular and functional markers for the prediction of therapeutic response.
Objective
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.
Fields of science
- 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)
Funding Scheme
RIA - Research and Innovation actionCoordinator
2333 ZA Leiden
Netherlands