Project description
Decreasing resistance to an important treatment for tuberculosis
Infectious diseases are caused by bacteria, viruses, fungi, and parasites. There are vaccines to prevent infection or medicines to kill the organisms but an increasing number of organisms are becoming resistant to treatments. Tuberculosis (TB) is caused by Mycobacterium tuberculosis. In many cases, these bacteria are resistant to multiple drugs, some with lethal results. The EU-funded TRIC-TB project is exploring a promising way to boost the effectiveness of treatment for multidrug-resistant TB. With a focus on restoring sensitivity to an existing line of treatment, scientists hope to improve patient outcomes regardless of initial resistance status at the time of infection.
Objective
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).
Fields of science
Programme(s)
Topic(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
4057 Basel
Switzerland
The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.