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

Periodic Reporting for period 2 - 3TR (Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions)

Período documentado: 2021-03-01 hasta 2022-08-31

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 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.
By the end of the second reporting period, 3TR has accomplished the design of all clinical protocols for the prospective observational studies with the final indications, and the recruitment of patients for these studies has started and is advancing. Several pipelines of work and analysis tools have been established at various fronts ranging from microbiome analyses, single cell work, Hyperion imaging and bioinformatics tools. The work has resulted in several publications which are accessible via the 3TR website (www.3tr-imi.eu).
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. 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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