Description du projet
Diminuer la résistance à un traitement important pour la tuberculose
Les maladies infectieuses sont causées par des bactéries, des virus, des champignons et des parasites. Il existe des vaccins pour prévenir l’infection ou des médicaments pour tuer les organismes, mais un nombre croissant d’entre eux deviennent résistants aux traitements. La tuberculose (TB) est causée par Mycobacterium tuberculosis. Dans de nombreux cas, ces bactéries sont résistantes à de multiples médicaments, certaines entraînant la mort. Le projet TRIC-TB, financé par l’UE, examine une solution prometteuse visant à stimuler l’efficacité du traitement pour la tuberculose multirésistante. En mettant l’accent sur la récupération de sensibilité à une ligne de traitement existante, les scientifiques espèrent améliorer les résultats pour les patients indépendamment du degré de résistance initiale au moment de l’infection.
Objectif
Tuberculosis (TB) is the world’s leading infectious disease. It killed 1.7 million people in 2016 and 10.4 million people developed active TB in the same year. In 2016, 480’000 of TB cases were multidrug-resistant (MDR-TB) and 9% percent of those cases are extensively drug-resistant (XDR), with mortality rates as high as 70%. Ethionamide (ETH) is a vital part of the WHO essential medicines list of 2nd-line TB therapy for MDR-TB, however, ETH suffers from significant levels of resistance and side effects at current dosing levels. BVL-GSK038 and BVL-GSK098 are proprietary to BioVersys/GlaxoSmithKline and have been developed through an extensive Lead Optimization program with collaborators from Lille University. Low doses of both compounds fully restore and “boost” the activity of ETH to rapidly kill Mycobacterium tuberculosis (Mtb) including MDR strains at significantly lower doses of ETH than previously reported, thus making MDR-TB sensitive to ETH once again. Through a comprehensive IND enabling package including in vitro and in vivo assessment of ETH with BVL-GSK038 and BVL-GSK098, including PK/PD, resistance development, safety, mechanism of action and synergistic studies with different drug compound combinations and then first in human clinical studies the consortium aims to:
i) Define the future placement of a boosted ETH (ETH + BVL-GSK038 or BVL-GSK098) in a universal TB treatment regimen, including overcoming MDR-TB with improved safety, time to cure and relapse rates;
Ultimately, we expect to identify a new and clinically proven TB regimen that leads to better patient outcomes independently of the starting resistance status of the TB infection. The TB and wider scientific communities will benefit from an improved understanding of ETH and the exploration of a novel class of therapeutic compounds acting on transcriptional modulators (BVL-GSK038 and BVL-GSK098).
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
RIA - Research and Innovation actionCoordinateur
4057 Basel
Suisse
L’entreprise s’est définie comme une PME (petite et moyenne entreprise) au moment de la signature de la convention de subvention.