Researchers have found that over-the-counter heartburn medications could shorten tuberculosis (TB) treatment.
TB typically takes months to treat, using a range of drugs. As a result, this can pose a challenge with completing treatment. To tackle this, shortening TB treatment is necessary to reduce the global burden of the disease.
A research team, led by Professor Lalita Ramakrishnan and colleagues from the University of Cambridge and the Medical Research Council Laboratory of Molecular Biology, Cambridge, analysed how common over-the-counter heartburn drugs could shorten TB treatment and why current treatment options need to be administered over a long period.
The research can be found in the Proceedings of the National Academy of Sciences (PNAS) journal.
TB affected 10.6 million people worldwide in 2021
Figures show that in 2021, around 10.6 million people worldwide contracted TB, and 1.6 million people died from the disease.
When people become infected, TB bacteria enter the tissues and invade cells that makeup part of the immune system, called macrophages. When they get there, they attempt to pump out the antibiotics used to improve the disease. This leads to the bacteria tolerating the antibiotics, elongating the process to treat TB.
Could heartburn drugs hold the answer to shortening TB treatment?
Heartburn drugs like omeprazole, pantoprazole, lansoprazole and rabeprazole are cheap, commonly available, safe, and already approved.
To start their investigation, the researchers decided to test if a cardiac and blood pressure drug called verapamil, which blocks human cell membrane pumps, could also be employed to block the bacterial cell membrane pump.
They used a neat approach where they tagged an antibiotic typically used for TB treatment, rifampicin, with a fluorescent marker so they could track exactly how the bacteria process the antibiotic. This meant they could directly see that verapamil does stop the bacteria from ejecting rifampicin.
The researchers then looked at whether other drugs used widely, which also block human cell membrane pumps, could have the same effect on the TB bacterial pumps as verapamil.
Professor Lalita 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.”
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 work was only carried out in cells, and more research is required to conduct clinical trials to look at potential treatment regimes for drug combinations in patients.
