Description du projet
Inhibition de la Janus kinase à base d’ARNsi dans le traitement des maladies inflammatoires de l’intestin
Les traitements actuels des maladies inflammatoires de l’intestin (MII) sont compromis par leur faible efficacité et leur mauvaise tolérance. Le projet NEW DEAL, financé par l’UE, entend mettre au point des thérapies nouvelles et radicales, plus efficaces et plus sûres pour tous les patients atteints de MII, en utilisant des inhibiteurs spécifiques des Janus kinases 1 et 3 (JAK1 et JAK3). Des études antérieures ont montré que les traitements à base d’ARNsi offrent une meilleure tolérance, notamment en termes d’immunogénicité, et la commodité d’une administration par voie orale. Axé sur la traduction clinique d’un produit basé sur les inhibiteurs de JAK, le projet vise à valider la sélectivité et la sécurité de l’inhibition. En outre, il sera question de l’administration locale de l’ARNsi dans l’intestin enflammé au moyen de transporteurs lipidiques nanostructurés innovants dotés de capsules polymériques pour la protection pendant le transit le long du tractus gastro-intestinal.
Objectif
Inflammatory bowel diseases (IBD) are the second most common immune-mediated disorders in Europe, affecting more particularly young people. The current therapies, including antibodies, show three main drawbacks: efficacy, tolerability and convenience. NEW DEAL solution will offer radical therapeutic progress for all IBD patients, thanks to the improved efficacy and increased safety of the specific JAK3 inhibition, which has been proven in clinics to be a target of great interest, the better tolerability of siRNA in term of immunogenicity and the good convenience with oral administration. To achieve this challenge, we will address three objectives: i) Specifically inhibit JAK 3 in a highly selective and safer manner by the mean of siRNA carefully designed and validated, ii) Deliver the siRNA therapeutic locally to the inflamed gut, by combining innovative nanostructured lipid carriers enabling their transport across the mucus, the intestinal barrier and the plasma membrane of the target cells, with polymeric capsules for protecting siRNA nanotherapeutics during their transit along the GI tract, thus allowing an oral administration, and iii) Promote the clinical translation and the future industrial transfer of this new clinical product, by addressing manufacturing, safety and efficacy evaluation at the late preclinical stage, to generate a Regulatory Submission Package and a Clinical Development Plan. The NEW DEAL project brings together clinical experts on IBD, leading scientists in nanomedicine, RNAi biology and immunology, innovative SMEs with a strong background in nanosafety, design of capsules and regulatory issues and an established pharma company with historic expertise on gastroenterology medicinal products. If successful, NEW DEAL will open new avenues for siRNA-based therapy in IBD with oral administration.
Champ scientifique
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugs
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- medical and health sciencesmedical biotechnologynanomedicine
- medical and health sciencesbasic medicineimmunologyimmunotherapy
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Régime de financement
RIA - Research and Innovation actionCoordinateur
75015 PARIS 15
France