Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause TB. Credit: NIAID, Flickr.
Although the vaccine for tuberculosis (TB) was developed more than a century ago, infections are on the rise with 7.3 million diagnosed cases recorded worldwide in 2018 — this is up from 6.3 million two years prior. Once the first symptoms of the infectious disease set in, the patient needs to undergo a lengthy treatment with a powerful cocktail of antibiotics, which isn’t foolproof.
This is where a promising new treatment pathway identified by researchers at the University of Manchester may come in. The team found a way to treat TB in animals with a non-antibiotic drug.
The treatment works by targeting Mycobacterium tuberculosis’ defenses rather trying to destroy the bacteria itself.
Mycobacterium tuberculosis secretes molecules called Virulence Factors, which block the immune system’s response to the infection, making it extremely difficult to combat it. This is why people need strong antibiotics, often over 6 to 8 months. But even after the treatment is over, there’s a 20% risk that the infection will resurface.
Professor Lydia Tabernero, the project’s lead researcher, and colleagues targetted a specific Virulence Factor called MptpB, which, when blocked, allows white blood cells to destroy the bacteria more efficiently. In trials, monotherapy with an orally bioavailable MptpB inhibitor reduced infection burden in acute and chronic guinea pig models.
“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,” Tabernero said in a statement.
Because MptpB isn’t found in humans, nor anything similar to it, the compounds used to block it are non-toxic to our cells.
What’s more, because the bacteria aren’t threatened directly, they are less likely to develop resistance against the treatment. Currently, the world is facing an antibiotic-resistance crisis that is threatening to undermine decades-worth of medical progress.
Scientists think that one in three people around the world is infected with TB, which kills 1.7 million annually. The disease is the most prevalent in Africa, India, China, but is on the rise in some western countries, particularly in the UK’s capital, London.
“TB is an amazingly difficult disease to treat so we feel this is a significant breakthrough,” said Tabernero.
”The next stage of our research is to optimise further the chemical compound, but we hope Clinical trials are up to four years away.”
The findings appeared in the Journal of Medicinal Chemistry.
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