Description du projet
Une thérapie combinée innovante pour la gestion de l’arthrose
L’arthrose est une maladie dégénérative qui touche toutes les articulations du corps et qui affecte des millions de personnes. Les interventions actuelles comprennent des médicaments analgésiques et anti-inflammatoires et des injections intra-articulaires de stéroïdes et d’acide hyaluronique (IA-HA), avec une efficacité modérée. Le projet SINPAIN, financé par l’UE, vise à comprendre l’arthrose afin de développer une réserve de thérapies basées sur les petits ARN interférents (siRNA) pour la prise en charge de l’arthrose du genou et un outil d’intelligence artificielle pour aider les cliniciens dans le diagnostic et le choix du traitement. Dans le cadre de ce projet, une nanoformulation d’IA-HA fonctionnelle chargée de vecteurs siRNA ciblant les voies de l’inflammation et de la douleur sera développée. Pour valider l’efficacité des cibles identifiées, des modèles de cellules humaines en culture 3D seront développés pour être testés dans des bioréacteurs imitant l’environnement et la biomécanique de l’articulation.
Objectif
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.
Champ scientifique
- 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
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Régime de financement
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinateur
20014 San Sebastian
Espagne