Tuberculosis is a major public health threat. In 2017 alone, over 10 million people developed active TB and it killed 1.7 million, making it one of the top 10 causes of death worldwide. Treatment is via a six-month course of four antibiotics. Drug resistance is a major issue in TB – in 2017, over half a million drug-resistant cases were recorded, and most of these (82 %) were multi-drug resistant (MDR); these cases are much harder to treat successfully. The aim of TRIC-TB is to advance the development of two molecules that could boost the infection-fighting ability of the anti-TB drug Ethionamide. The compounds, BVL-GSK038 and BVL-GSK098, work by interfering with the systems that control gene activity in the TB bacteria. Previous studies have shown that they are able to boost the efficacy of Ethionamide three-fold. If the results are confirmed in humans, this could allow doctors to reduce the dose of Ethionamide typically given to patients, something that would also reduce the side effects associated with the drug. Moreover, it appears that BVL-GSK038 and BVL-GSK098 overcome some of the mechanisms that the TB bug has developed against Ethionamide. TRIC-TB will carry out further research in areas such as safety, mechanism of action, and potential synergies with other drugs; if these go well, the team will carry out the first clinical studies in humans of these potential drugs. Ultimately, the information delivered from this research will hopefully allow the new compounds to be integrated into new, improved regimens to treat TB, including MDR-TB.
TRIC-TB is part of the IMI AMR Accelerator Programme.