Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions

Informations projet

3TR

N° de convention de subvention: 831434

DOI

10.3030/831434

Date de signature de la CE 22 Août 2019

Date de début 1 Septembre 2019

Date de fin 31 Août 2026

Financé au titre de

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coût total

€ 87 721 177,75

Contribution de l’UE

€ 40 273 191,50

Coordonné par

FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUD M.P.
Spain

Periodic Reporting for period 4 - 3TR (Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions)

Période du rapport: 2024-03-01 au 2025-08-31

Résumé du contexte et des objectifs généraux du projet

Patients from several immune-mediated diseases experience continued trial-and-error testing of new drugs without adequate selection based on personalized molecular patterns of disease. In consequence, the patients suffer from not having an adequate response to the therapy they are given, causing perpetuation of tissue damage or even death. The main objective of 3TR is therefore to define the molecular mechanisms behind this therapeutic unresponsiveness in patients from 7 different immune-mediated diseases, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, asthma, chronic obstructive pulmonary disease and inflammatory bowel disease - diseases that affect important portions of the European population. As secondary objectives, 3TR has as the goal to define new therapeutic targets through the molecular stratification of patients according to their tissue molecular structure and to define biomarkers that can be used in the future to design personalized therapies. Finally, 3TR will also identify the mechanisms behind the appearance of the biomarkers using novel methodologies such as tissue organoids. The results will have a major impact in the society, as it will lead to a more personalized approach towards therapy and reduce severe tissue damage and invalidation.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

By the end of the fourth reporting period, 3TR has accomplished 100% recruitment of the patients in most of the prospective observational studies. The operations management team, created to ensure the flow of the pipeline from sample to data continuous its work. In this flow, a large volume of patient samples have been sequenced and genotyped. Working groups for the analyses of single cell data, in the form of scRNASeq, mass cytometry or imaging have set up their tools and necessary materials to begin receiving tissue samples. In addition, data from industry clinical trials have been uploaded and results are presented. Samples from prior existing studies and trials have been included in the pipelines and are also sequenced. Across disease analysis plans have been agreed and analyses have started. The work has resulted in several publications which are accessible via the 3TR website (www.3tr-imi.eu).

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

We expect to identify the molecular patterns and the mechanisms behind the unresponsiveness to the therapies given to patients of 7 different immune-mediated diseases. We will also identify biomarkers for severity and activity for each of them but also biomarkers that may allow their use across diseases and the mechanisms that may overlap between them. In addition, we will define the mechanisms of action of some of the drugs and their activity in certain patients and not others through in vitro organoid studies that will be feasible to do in the prospective studies, particularly in the case of the IBDs.
These studies will help to improve the approaches to personalized medicine by arming frontline healthcare providers with more information to place patients on the right treatment at the right time. This will reduce the severity and damage of the disease by choosing the best treatment option right from the start. In consequence, the results of 3TR will reduce the costs of pharmacotherapy and the burden of a suboptimal treatment by helping to avoid them.
Finally, the results of this project will offer economic opportunities to European companies to exploit those results e.g. for the development of biomarker test kits. 3TR will therefore have an important social and economic impact in Europe.

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