Projektbeschreibung
Innovative Kombinationstherapie zur Behandlung von Osteoarthrose
Osteoarthrose ist eine degenerative Erkrankung, die alle Gelenke des Körpers betrifft. Millionen Menschen leiden darunter. Zu den derzeitigen Interventionen zählen Schmerzmittel, entzündungshemmende Medikamente und intraartikuläre Injektionen von Steroiden und Hyaluronsäure (IA-HA), die nur mäßig wirksam sind. Das EU-finanzierte Projekt SINPAIN zielt darauf ab, die Osteoarthrose zu verstehen, um ein Repertoire an Therapien auf der Grundlage von „kurzer interferierender RNA“ (small interfering RNA, siRNA) für die Behandlung der Knie-Osteoarthrose sowie ein KI-Instrument zu entwickeln, das medizinischen Fachkräften bei der Diagnose und der Behandlungswahl hilft. In diesem Rahmen wird eine Nanoformulierung von funktionellem IA-HA entwickelt, die mit auf Entzündungs- und Schmerzwege abzielenden iRNA-Vektoren beladen ist. Zur Validierung der Wirksamkeit der identifizierten Zielmoleküle werden menschliche Zellmodelle in 3D-Kultur entwickelt, die in Bioreaktoren getestet werden, welche die Umgebung und Biomechanik des Gelenks nachahmen.
Ziel
According to the WHO Osteoarthritis (OA) is one major course of years lived with disability in the elderly and considered a high burden disease, which makes it a research priority in Europe. There is no cure for OA and SoA treatments need to be reconsidered. Current pharmacological interventions consist of analgesic, anti-inflammatory drugs as well as intraarticular steroids and hyaluronic acid (IA-HA) with moderate efficacy and associated long-term side effects. New medications are thus needed both to alleviate pain and slow down disease progression. Taking advantage of the explosion of RNA technologies in the last years, SINPAIN aims to develop a pipeline of siRNA-based therapy built on the combination of current technologies (dyanmic IA-HA and nanocarriers) that will be designed step-by-step in order to reach a successful management of inflammation and innervation therapy for the treatment of early (grade 0-1) and later stages (grade 3-4) of knee osteoarthritis (OA). To do so, a nanoformulation composed of functional IA-HA that can be loaded with vectors, for the delivery of siRNA targeting IL1? and NGF, and nanocarriers will be developed. In parallel, large effort will focus on understanding the pathological mechanisms of OA. To validate efficacy in relevant potency assays, 3D coculture models will be developed with human cells and tested in unique bioreactors mimicking joint environment and biomechanics. With the identified cell targets, IA-HA will be modified with immunomodulator peptide which will activate the adaptive immune response, responsible for OA regeneration. The 4 pipeline products of SINPAIN will be validated in vivo in a relevant OA model with SoA techniques that will demonstrate the reduced inflammation and pain, as well as the cartilage regeneration for the last product. Taking advantage of all the data obtained during the project, a decision-making tool based on machine learning will be validated to offer patients a personalized therapy.
Wissenschaftliches Gebiet
- engineering and technologyenvironmental biotechnologybioremediationbioreactors
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesmedical biotechnologynanomedicine
- natural sciencescomputer and information sciencesartificial intelligencemachine learning
Schlüsselbegriffe
Programm/Programme
Aufforderung zur Vorschlagseinreichung
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HORIZON-RIA - HORIZON Research and Innovation ActionsKoordinator
20014 San Sebastian
Spanien