Authors: Georgi Makin (Future Science Group)
Scientists at the University of Manchester (UK) have developed the first non-antibiotic drug to successfully treat tuberculosis (TB) in animal trials.
In a novel approach to fighting bacteria, the team has focused on targeting Mycobacterium tuberculosis’ defenses, rather than attacking the bacteria, which may have an advantage against antibiotic resistant strains.
The study, published in the Journal of Medicinal Chemistry, describes the drug’s success in guinea pigs for both acute and chronic TB.
“The fact that the animal studies showed our compound, which doesn’t kill the bacteria directly, resulted in a significant reduction in the bacterial burden is remarkable,” explained Lydia Tabernero (University of Manchester, UK), project leader. “For more than 60 years, the only weapon doctors have been able to use against TB is antibiotics. But resistance is becoming an increasingly worrying problem and the prolonged treatment is difficult and distressing for patients. With current treatments, there’s no guarantee the disease will be eliminated: antibiotics do not clear the infection and the risk of being infected with drug-resistant bacteria is very high. But by disabling this clandestine bacteria’s defenses we’re thrilled to find a way that enhances the chances of the body’s immune system to do its job, and thus eliminate the pathogen,” Tabernero continued.
The team identified virulence factor, MptpB, as a suitable target for the novel drug. By blocking the virulence factor, white blood cells are able to destroy TB more efficiently and effectively.
“The great thing about MptpB is that there’s nothing similar in humans – so our compound which blocks it is not toxic to the human cells,” Tabernero added. “Because the bacteria haven’t been threatened directly, it is less likely to develop resistance against this new agent, and this will be a major advantage over current antibiotics, for which bacteria had already become resistant. TB is an amazingly difficult disease to treat so we feel this is a significant breakthrough. The next stage of our research is to optimize further the chemical compound, but we hope Clinical trials are up to four years away.”
Sources: Vickers CF, Silva APG, Chakraborty A et al. Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo. J. Med. Chem. doi: 10.1021/acs.jmedchem.8b00832. (2018) (Epub ahead of print); www.eurekalert.org/pub_releases/2018-09/uom-sdn091018.php