NZ know-how helps in TB drug success

Drug treatment limited the spread of TB on zebrafish larvae.

International research with its roots in Auckland has produced a breakthrough that could yield a new type of drug treatment for tuberculosis.

The experiments on tropical zebrafish found that granulomas - lumps caused by TB bacteria - create their own network of blood vessels in a process called angio-genesis. This also occurs in tumours and the researchers tested - in zebrafish larvae - expensive, biological medications that disrupt human cancers' blood-vessel-forming mechanisms.

The drug treatment reduced the infection burden and limited the spread of TB within the fish larvae, say the researchers, whose paper is published today in Nature, the world's top scientific journal.

They say this opens a new line of research for others to find inexpensive drugs targeting blood vessel formation in granulomas.

One of the scientists, Professor Philip Crosier, of Auckland University, said it would be unrealistic to use costly cancer drugs for the widespread treatment of TB.

"But this discovery presents the opportunity to screen for cheap, small molecules that might do the same job as the biological agents.

"The formation of these granulomas that we can model in zebrafish are almost identical to what you would see in humans. As the fish are transparent, the granulomas that form on the exterior surface of the zebrafish can be easily visualised."

Professor Crosier was an adviser on the experiments, which were conducted at Duke University in the United States.

The project, a progression of work that started in his laboratory, was led by Duke's Dr Stefan Oehlers, who gained his doctoral degree at Auckland University. It arose from discussions about blood vessels and TB involving a third researcher, Dr Kazuhide Okuda, who also gained his doctorate at Auckland.

"I have quite a bit of experience in vascular biology and we concluded that this was something worth exploring," said Dr Okuda.

"We have created a 3D structure view of how the TB granuloma works and this was important because it's better for visualising how the angio-genesis happens and shows that it happens equally in arteries and veins."

What is tuberculosis

What is tuberculosis?

An infectious disease caused by the bacterium called mycobacterium tuberculosis and spread by coughed and sneezed droplets.

How big a problem is it?
Last year it made 9 million people ill and killed 1.5 million worldwide. Most TB deaths occur in low and middle-income countries. New Zealand had 294 notified cases in 2012, of whom four died.

What is the discovery?
Tropical fish embryos were infected with a fish version of TB. It caused lumps called granulomas to form on their surface. In human TB they can form in the lungs. The findings showed that the granulomas created a network of blood vessels and that cancer drugs which targeted blood-vessel development limited the spread of infection.

Why zebrafish?
Their organ systems have similarities to those in humans. They are easy to study because they are transparent. Introduced genes make the granulomas and blood vessels show up as different colours, allowing identification through a microscope.