Glaucoma Drug Appears to Fight TB

By Jane Farrell

A medicine used for glaucoma could also be used to treat tuberculosis – even the drug-resistant kind, research shows.

Robert Abramovitch, a Michigan State University microbiologist, along with graduate student Benjamin Johnson, have discovered that ethoxzolamide, a sulfa-based compound found in many prescription glaucoma drugs, actually turns off the bacterium’s ability to invade the immune system.

The finding was published in the journal Antimicrobial Agents and Chemotherapy.

“Basically, ethoxzolamide stops TB from deploying its weapons…shutting down its ability to grow inside certain white blood cells in the immune system,” Abramovitch said. “We found the compound reduces disease symptoms in mice.”

He also said that TB has the ability to sense environmental cues in the body – and adapt accordingly. One of these cues includes the infection’s ability to detect pH – or acidity levels – which tells the disease it’s being attacked by a host immune cell.

“The compound we found inhibits TB’s ability to detect acidic environments, effectively blindfolding the bacterium so it can’t resist the immune system’s assault,” Abramovitch said.

It’s estimated that 2 billion people, globally, carry the infection, but in most cases it lies dormant and the immune system is able to prevent it from spreading in the body.

But, he cautioned, there are some limitations. “It’s a standoff. The immune system has difficulty clearing the infection and the TB bacterium is just waiting for the immune system to weaken.”

Abramovitch and his research team screened 273,000 different compounds in hopes of finding one that could possibly stop the disease. By using a synthetic biosensor that glows green in response to conditions that mimic TB infection he eventually found the needle in the haystack that turned the bacterium’s sensing ability off.

Yet, this elusive compound not only has the potential of preventing the disease from spreading, but Abramovitch suggests that it could help shorten the length of treatment and slow the emergence of drug resistance, particularly if found to work in conjunction with other existing TB drugs. Current treatments can last up to six months.

“The single biggest reason for the evolution of drug-resistant strains is the long course of treatment,” Abramovitch said. “It’s difficult for a patient to complete the entire antibiotic course required to kill all of the bacteria. Shortening the duration will help slow the development of these resistant strains.”