Common heartburn drugs could shorten months of treatment for TB patients, Cambridge scientists discover
Over-the-counter drugs that are commonly used to treat heartburn could shorten the treatment of tuberculosis (TB), Cambridge scientists have discovered.
They found the drugs could also cut the chances of the bacteria that causes TB from becoming drug resistant.
It is hoped the findings could mean TB can be cured with shorter treatments, which typically takes months to treat with multiple drugs - something that proves logistically complicated for many people.
It is estimated that 10.6 million people worldwide fell ill with TB and 1.6 million people died from the disease in 2021.
The research was led by TB research pioneer Prof Lalita Ramakrishnan and colleagues from the University of Cambridge and the MRC Laboratory of Molecular Biology in Cambridge, who wanted to explore why long antibiotic treatments are usually required.
It is known that when TB bacteria enter our tissues and invade immune system cells called macrophages they turn on pumps in their cell membranes that push out the antibiotics we use against them. This leaves the bacteria tolerant to the antibiotics.
The researchers tested whether a cardiac and blood pressure drug called verapamil, which blocks human cell membrane pumps, was also able to block the bacterial cell membrane pump.
They tagged an antibiotic used to treat TB, rifampicin, with a fluorescent marker to track how the bacteria process the antibiotic. It showed directly that verapamil does indeed stop the bacteria ejecting rifampicin.
They then tested whether drugs in wide use for other conditions that also incidentally block human cell membrane pumps could have the same effect.
Prof Ramakrishnan said: “That’s when my PhD student, Alex Lake, decided to screen these drugs and bingo, many of them worked.
“The most stunning of all was the class of proton pump inhibitors that are among the most widely used, over the counter drugs for heartburn, reflux, gastritis - omeprazole, pantoprazole, lansoprazole, rabeprazole.
“Not only do they work, but they work as well as or possibly with even greater potency than verapamil.
“This is very cool, because one of the holy grails of TB treatment is can we come up with shortening regimes.
“And since active drug pumps are thought to enable bacteria to develop drug resistance, there is a possibility that these drugs could at the same time reduce the chances of drug resistance, a significant problem in TB treatment.”
The study, published in Proceedings of the National Academy of Sciences (PNAS) on Monday, has so far only been carried out in cells and more research will be needed before clinical trials could examine potential treatment regimes using drug combinations for patients.
Dr Stephen Oakeshott, head of infection and immunity at the Medical Research Council, part of UK Research and Innovation, said: “This exciting work is a great example of how understanding basic cellular mechanisms can directly unlock pathways to future treatment regimes.
“The potential for repurposing cheap and easily accessible drugs to accelerate TB treatment could have enormous health impact worldwide and we look forward to seeing this discovery move forward.”
The scientists collaborated with researchers in Italy and in the US on the work.
