Projektbeschreibung
Kombinatorischer Ansatz zur Behandlung immunvermittelter entzündlicher Krankheiten
Als immunvermittelte entzündliche Erkrankungen (immune-mediated inflammatory diseases, IMID) wird eine Gruppe heterogener Autoimmunerkrankungen mit zum Teil ähnlicher molekularer und zellulärer Symptomatik bezeichnet. Dazu gehören u. a. rheumatoide Arthritis, Psoriasis, Morbus Crohn, Colitis ulcerosa und systemischer Lupus erythematodes. Um die Prognosen bei immunvermittelten entzündlichen Krankheiten deutlich zu verbessern, soll das EU-finanzierte Projekt DocTIS wirksame kombinatorische Therapien ermitteln und untersuchen, welche Patientengruppen optimal auf die Behandlung ansprechen. Anhand von Proben aus IMID-spezifischen Biobanken und mit Hochdurchsatztechnologien sollen neue molekulare Daten gewonnen werden. Mit systembiologischen Methoden werden Modelle von Reaktionen auf gezielte Therapien generiert und Prognosen zu optimalen synergistischen Wirkstoffkombinationen erstellt. Für einen Konzeptnachweis wird nach der präklinischen Phase die optimale kombinatorische Therapie an einer Patientengruppe mit positivem Biomarkerprofil getestet.
Ziel
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.
Wissenschaftliches Gebiet
- medical and health sciencesclinical medicinerheumatology
- medical and health scienceshealth sciencesinflammatory diseases
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- medical and health sciencesbasic medicineimmunologyautoimmune diseases
- medical and health scienceshealth sciencespersonalized medicine
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenUnterauftrag
H2020-SC1-2019-Two-Stage-RTD
Finanzierungsplan
RIA - Research and Innovation actionKoordinator
08035 Barcelona
Spanien