Descrizione del progetto
Inibizione della Janus chinasi basata su siRNA (RNA interferente breve) nel trattamento delle malattie infiammatorie intestinali
Gli attuali trattamenti per le malattie infiammatorie intestinali sono pregiudicati dalla scarsa efficacia e dalla bassa tollerabilità. Il progetto NEW DEAL, finanziato dall’UE, intende sviluppare terapie nuove e radicali che presentino un’efficacia e una sicurezza per tutti i pazienti affetti da malattie infiammatorie intestinali, utilizzando inibitori specifici delle Janus chinasi 1 e 3 (JAK1 e JAK3). Studi precedenti hanno dimostrato che i trattamenti a base di siRNA offrono una tollerabilità migliore, soprattutto in termini di immunogenicità, nonché la comodità di una somministrazione per via orale. Concentrando l’attenzione sulla traduzione clinica di un prodotto basato sugli inibitori di JAK, il progetto si prefissa di convalidare la selettività e la sicurezza dell’inibizione. Inoltre, affronterà il tema della consegna locale di siRNA all’intestino infiammato grazie a innovativi vettori lipidici nanostrutturati, con capsule polimeriche che li proteggano nel transito lungo il tratto gastrointestinale.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
Argomento(i)
Invito a presentare proposte
Vedi altri progetti per questo bandoBando secondario
H2020-NMBP-2016-two-stage
Meccanismo di finanziamento
RIA - Research and Innovation actionCoordinatore
75015 PARIS 15
Francia