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DECISION ON OPTIMAL COMBINATORIAL THERAPIES IN IMIDS USING SYSTEMS APPROACHES

Project description

DEENESFRITPL

Combinatorial therapy for treatment of immune-mediated inflammatory diseases

Immune-mediated inflammatory diseases (IMIDs) represent a group of heterogeneous autoimmune disorders with some common features at molecular and cellular level; they include rheumatoid arthritis, psoriasis, Crohn’s disease, ulcerative colitis and systemic lupus erythematosus. The EU-funded DocTIS project aims to dramatically improve the prognosis of IMIDs by identifying effective combinatorial therapies as well as which patient groups show optimal response to treatment. Using samples from biobanks specialised in IMIDs, new molecular data will be obtained using advanced high-throughput technologies. Systems biology methods will be applied to model responses to targeted therapies and predict what drug combinations will act synergistically. To provide proof of concept, after the preclinical stage, the optimal combinatorial therapy will be tested in a group of patients with a positive biomarker profile.

Objective

Immune-Mediated Inflammatory Diseases (IMIDs) are a group of common autoimmune diseases that include clinically heterogeneous disorders such as rheumatoid arthritis, psoriasis, psoriatic arthritis, Crohn’s disease, ulcerative colitis and systemic lupus erythematosus. Despite their clinical heterogeneity, IMIDs share a significant number of features at the molecular and cellular levels. Recently developed therapies targeting common key molecules of the immune system like anti-TNF agents, have collectively resulted in a significant improvement in the management of IMIDs. Still, the complete control of the chronic inflammatory process is rarely attained, and too many patients experience a poor response, if at all. This inefficacy has become a major economic burden and severely impacts on the wellbeing of many European citizens. The DocTIS projects aims to profoundly change this trend by identifying highly effective combinatorial therapies as well as the group of patients where this response will be optimal. Using the standardized samples from one of the world’s largest biobanks specialized in IMIDs, new molecular data will be generated using advanced high-throughput technologies including single cell RNA-seq. Systems biology methods will be applied to this unique clinical and molecular data to model the response to targeted therapies and predict what drug combinations will act synergistically and on which types of patients. After validation in a preclinical stage, the optimal combinatorial therapy will be tested in a group of patients with a positive biomarker profile. Using a basket trial, a new type of clinical trial design that incorporates molecular marker information, the DocTIS project will provide proof of concept of the utility of combinatorial therapy and personalized medicine for the effective control of disease activity in IMIDs.

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Call for proposal

H2020-SC1-BHC-2018-2020

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Sub call

H2020-SC1-2019-Two-Stage-RTD

Funding Scheme

RIA - Research and Innovation action

Coordinator

FUNDACIO HOSPITAL UNIVERSITARI VALL D'HEBRON - INSTITUT DE RECERCA
Net EU contribution
€ 1 079 085,00
Address
Passeig vall d hebron 119-129 edificio de recerca
08035 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Other funding
€ 0,00

Participants (10)

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Last update: 10 March 2023
Record number: 226455

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European Union, 2023