Targeting tubulins

The initial spark for the project to develop drugs for use against parasites goes back 18 years, when Murdoch University's Thompson's first discovered that a particular drug used against intestinal worms was also very effective against Giardia intestinalis, the single cell parasite that causes Giardiasis, a common diarrheal illness prevalent throughout the world.

What Thompson found was, in fact, a new indication for the drug, albendazole, currently marketed around the world as Zentel.

"From a research point of view that got us thinking: why is albendazole so good against Giardia? What is it targeting in the parasite? Is it the same target as in the worms?" Thompson says.

Thompson soon discovered that the target was indeed the same. The solution lies in microtubules, one of the components of the cytoskeleton of these kinds of parasitic organisms. According to Thompson, Epichem's compounds target tubulins, the globular proteins that help to make up microtubules.

The next step was to find out whether albendazole and similar drugs were as effective against other protozoa as they were against Giardia. "That was when we formed the relationship with Wayne and we started to make drugs that were focused on this target that albendazole focused on," Thompson says. "Today, we're looking at a whole stable of compounds that affect these different parasites."

Currently, Epichem's synthetic compounds are still in the preclinical phase and have yet to be tested on humans. The lead compound has shown itself to work in a validated mouse model, which Best and Thompson claim is a reliable indicator of treating the disease in humans.

The compounds have also undergone a number of sophisticated toxin studies - in vivo, oral toxicity, Ames test - and they appear unlikely to be carcinogenic or mutagenic. Best also claims that compound is very cheap to make, which is rather important with this type of disease.

"If we had to start this work as part of Epichem, we'd be hard pressed to justify why Epichem is doing it," Best says. "But we've managed to keep this project alive and finally after all these years it is getting properly funded and is going somewhere.

"The fact that it could potentially cure a really horrible disease, that's a great buzz," he says. "Being able to say we've been involved in getting a drug to marketplace that can save millions of lives would be a great feeling for a small company like us."