| Project Title | Experimental model of peripheral mononuclear cells serum biomarkers for cladribine treatment response in patients with relapsing-remitting multiple sclerosis: a step toward personalized treatment. |
| Project Registration Code | MULTIPLE SCLEROSIS INNOVATION REGIONAL GRANT FOR CENTRAL AND EASTERN EUROPE COUNTRIES 2017- financed by MERCK EMD SERRONOCONTRACT NUMBER: 584/2018 |
| Project Acronym | CEE GRANT |
| Purpose and project planning | Objectives: 1.This ex vivo and in vitro study was designed to investigate Cladribine’s effects on PBMC function after the removal of Cladribine, to distinguish cytotoxic versus immunomodulatory effects of this DMT, in order to anticipate the treatment effect in a personalized manner; 2. Better knowledge of PBMC isolation, expansion and behavior will help creating an algorithm of responsiveness to other DMTs in order to choose the best therapy for each patient avoiding cerebral tissue loss, handicap accumulation and financial wastage.Currently, relying on our previous research in the field of MS immunopathology and the scientific data from the literature, we aim to make the transition from the study of the peripheric cytokine secretion profile of the Th17 cells of MS patients, to assessment of a higher direct resolutive peripheric secretor profile of PBMC and, most importantly, to the determination of phenotypic cellular changes in these cells together with the characterisation of the cytokines secreted in the presence of a certain DMT. Starting from the concept that there are NR to DMTs among MS patients, our target is to initiate, assess and demonstrate the accuracy of an experimental method, in order to find appropriate biomarkers for the early prediction of the responsiveness of the MS patient to Cladribine but this model might be extended to any other DMT. As part of a personalized therapy algoritm, these predictive biomarkers will permit the early shift towards a more efficient personalised therapy.Novelty of the project. There are no published data concerning the ex vivo and in vitro effect of Cladribine on PBMC fynotype and on PBMC secretion (using a costom made cytokine panel) after exposure to Cladribine. Therefore, we want to assess an experimental method for the isolation, culture and expansion of PBMN cells in our laboratory, followed by the study of in vitro Cladribine effects on PBMC differentiation and the antiinflammatory shift of secreted cytokines. |
| Project Start Date | 01 Jan 2019 |
| Project End Date | 31 Dec 2020 |
| Project Duration | 24 months |
| Total budget value | 100000 euro |
| Team: | Name | Role |
| PROF. DR. BĂLAȘA RODICA | PROJECT DIRECTOR |
| PROF. DR. MINODORA DOBREANU | RESEARCHER |
| | DOINA MANU | POSTDOCTORAL RESEARCHER |
| | ADINA HUȚANU | POSTDOCTORAL RESEARCHER |
| | SMARANDA MAIER | POSTDOCTORAL RESEARCHER |
| | OLAH PETER | POSTDOCTORAL RESEARCHER |
| Potential Results | A thorough knowledge of a drug’s mechanism of action that allows an optimization of effect, a major reduction of side effects and is a step toward finding new biomarkers. |
| Conferences | Rodica Bălașa, Doina Manu, Andreea Romaniuc, Minodora Dobreanu. Experimental model of isolation, cultivation and exposure to cladribine of T lymphocytes from multiple sclerosis patients: a step toward personalized treatment. https://onlinelibrary.ectrims-congress.eu/ectrims/2019/stockholm/ 278837/ rodica.balasa.experimental.model.of.isolation.cultivation.and.exposure.to.html |
| Publications | Balasa R, Barcutean L, Balasa A, Motataianu A, Roman-Filip C, Manu D. The action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitis. Hum Immunol. 2020 May;81(5):237-243. doi: 10.1016/j.humimm.2020.02.009. Epub 2020 Feb 28. PMID: 32122685.Balasa R, Maier S, Barcutean L, Stoian A, Motataianu A. The direct deleterious effect of Th17 cells in the nervous system compartment in multiple sclerosis and experimental autoimmune encephalomyelitis: one possible link between neuroinflammation and neurodegeneration. Rev Romana Med Lab. 2020;28(1):9-17. DOI:10.2478/rrlm-2020-0005Manu D. et al. Treatment with cladribine selects T17.1 cells in RRMS patients – an in vitro study. 2021. In press |
| Host institution | ”George Emil Palade” University of Medicine, Pharmacy, Sciences and Technology of Târgu Mures |
| Protocol | Detailed experimental protocol |
| Articles | THE action of TH17 cells on blood brain barrier in multiple sclerosis and experimental autoimmune encephalomyelitisThe direct deleterious effect of Th17 cells in the nervous system compartment in multiple sclerosis and experimental autoimmune encephalomyelitis: one possible link between neuroinflammation and neurodegeneration |
