Scientist hopes to stop deadly TB

Otago University microbiologist Greg Cook says the drug could eradicate the disease in New Zealand.

Research finds medicine could be repurposed against drug-resistant strain with promise for Third World.

A leading New Zealand researcher may have found a powerful new weapon to combat deadly, drug-resistant strains of tuberculosis, hidden in a drug that's been used elsewhere for decades.

Otago University microbiologist Professor Greg Cook is investigating if derivatives of amiloride, a diuretic long used for hypertension and congestive heart failure, could hold the key to stopping strains of TB from fighting drugs.

Around the world, resistant TB strains are becoming of increasing concern to scientists; of the 1.5 million people killed by TB every year, more than 200,000 had contracted a form that antibiotics could not kill.

"We have 10 million new cases of TB every year, and of those, five per cent are drug-resistant strains," Cook said.

In developing nations, the rate was much higher, reaching 40 per cent in China and 20 per cent in India.

"And, of course, these people are immigrating here - 75 per cent of all TB in New Zealand is from people who are born overseas - so these strains find their way into our country."

For those hard-to-kill strains, treatment is lengthy and expensive.

In one recent instance, clinicians at Dunedin Hospital who saved the life of a patient went through nine drugs before they cured him. The process cost $180,000.

Cook believed there was an urgent need to develop a new generation of drugs powerful enough to combat these new strains.

A decade ago, Cook and his team pin-pointed the activating process in a major enzyme of the bacterium (mycobacterium tuberculosis) responsible for tuberculosis.

Around the same time, a team of scientists discovered bedaquiline, trade name Sirturo, which gave the world its first new medicine for TB in more than 40 years.

Patients with drug-resistant TB had typically had to take medication for between one and two years. Bedaquiline slashed treatment to just eight weeks in clinical trials, as it effectively shut down the energy-generating machinery of mycobacterium tuberculosis.

That breakthrough led Cook to amiloride, which had molecular features resembling those of bedaquiline.

"We tested amiloride, and though it was a very weak inhibitor, nonetheless it was actually able to kill TB," he said.

"So we've taken a molecule that was already a good drug, we've made some modifications to it, and now we can show we can use it against TB."

The diuretic, which is designed to spare potassium in the body and has been around since 1967, also had potential uses against cancer.

Cook said a major strength of amiloride as an anti-TB agent was that it could be taken orally, making it much more suitable for use in Third World countries.

While there remained disproportionately high rates of TB among Maori and Pacific populations, he saw an opportunity to use these new drugs to rid New Zealand of the disease.

"We could lead the world because we've got such a low incidence rate and could actually eliminate TB, although, to do that, we'd still need to reduce our incidence by 70-fold."

Cook has received a three-year grant from the Health Research Council to take his lab-based amiloride findings further.

"We're already a long way down the track, and I'd expect that in the next one to two years, we are going to know if this is going to treat TB in some form of animal model."

Tuberculosis

• Tuberculosis (TB) is a bacterial infection that most commonly affects the lungs, but can also affect the lymph nodes, bones, joints and kidneys. It can cause meningitis.

• In New Zealand, there are approximately 300 cases of TB diagnosed each year. While life-threatening complications such as haemorrhage from the lungs are now rare, TB can still be a very serious disease, particularly for older people.

• Around the world, however, and particularly in Third World nations, TB kills 1.5 million people every year, of whom 200,000 contract drug-resistant strains.