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04/29/2009

'Model tumours' to cut costs and risks of cancer drug discovery

Griffith University Associate Professor Vicky Avery and Dr Gregory Fechner have secured almost $300,000 from the Prostate Cancer Foundation of Australia for a unique project designed to reduce the cost and risks associated with developing and testing new cancer drugs.

Prostate cancer is the most commonly diagnosed cancer in men. In Australia each year 18,700 men are diagnosed and approximately 3000 deaths result from this cancer.

Assoc Professor Avery said the project was to develop three-dimensional tumour models for testing potential new tumour drugs. The models would consist of prostate cancer cells grown, imaged and analysed in 3D. This would provide researchers with a tool to determine whether compounds had the ability to penetrate the tumour mass along with evidence of its effectiveness, providing valuable information well before clinical trials.

"Developing a new drug is a long, risky and expensive process that costs an estimated US$802 million per drug and takes an average of 12.8 years. For every new drug there are many which have not been successful. If we can select promising drug compounds early on we may be able to speed the process," she said.

The project will involve creating tumour models which are representative of the different stages of disease progression.

"Normally we test drugs on cancer cells in a two-dimensional environment on a flat surface, but this doesn't take into consideration the complexities of the real tumour environment in the living patient. We need to show how, and if, the potential drug penetrates the tumour or how it impacts on the cell-to-cell interactions."

While this level of analysis is normally a slow and arduous process, Assoc Professor Avery’s team aims to develop an automated means of analysing these 3D tumour models.  Imaging systems currently in use which allow high-throughput screening of complex cellular interactions will be further developed for this application.

She said the project could prove particularly effective in identifying and progressing new therapeutic compounds for the treatment of later-stage cancers that are unresponsive to current treatments. There is a great need for treatments which are effective against metastatic prostate cancer which spreads to other parts of the body, such as the bone and lymph nodes.

"We hope that this project will help to reduce both cost and risk involved in early-stage drug development and may have wider reaching applications within cancer research."

Associate Professor Avery is a drug development leader at Griffth University's Eskitis Institute for Cell and Molecular Therapies.


Australians on alert as swine flu spreads

Leading Griffith University Researcher, Mark von Itzstein, has urged people to remain calm in response to news the deadly swine flu is already on Australia’s doorstep.

The new influenza strain, feared to have killed 81 people in Mexico and infected 10 in the US, has "pandemic potential", the World Health Organisation (WHO) warned on Sunday.

Ten New Zealand students just returned from Mexico have tested positive for influenza A and are believed "likely" to have contracted swine flu, placing it close to Australian shores.

Three teachers and 22 senior students from Auckland's Rangitoto College were kept in isolation after they returned from Mexico on Saturday after a three-week language trip with flu-like symptoms.

Professor von Itzstein said the latest virus had come out of left field and was spreading more quickly than the avian strain.

It’s now a virus that has infected and killed a significant number of people, so it’s aggressive, that’s quite clear," Professor von Itzstein said.

"Like bird flu we have to be cautious, but not overreact.

"But the fact is this virus looks as though it has developed to be able to infect humans rapidly."

Professor von Itzstein said swine flu could be easily spread through travel.

"There’s no doubt about that. People flying from Mexico to Australia could deliver the virus right to our shores and individuals may not know that they have the infection, that’s why it’s a concern," he said.

"But the authorities have systems in place."

Professor Mark von Itzstein’s laboratory discovered the first anti-influenza drug in the world—Relenza. 

Relenza is stockpiled throughout the world to defend against influenza outbreaks, and more importantly, it also is effective in treating the swine flu.


Ancient Australian remedy as novel pain killing drugs

The quest to develop novel pain-killing drugs from a native Australian plant, traditionally used by Aboriginal people, is a step closer with a new partnership between Queensland’s Griffith University, JJ Lab Pty Ltd and Avexis Pty Ltd.

Griffith researchers and the Western Australian Kimberley region’s Nyikina and Mangala Nations’ peoples have worked together to identify active drug-like compounds from traditional Aboriginal medicine.

The University and the Aboriginal community, through its company JJLab, today signed a license agreement with biotech startup venture Avexis to further develop pain-killing drugs based on research that shows the Marjarla plant contains a novel class of analgesic compounds.

Griffith’s Eskitis Institute Director Professor Ron Quinn said the plant showed considerable promise for development as a natural remedy and a suite of new pharmaceutical medicines.

“I first learned of the plant's analgesic potential after hearing about and then meeting an Aboriginal man in the Kimberley region whose finger had been bitten off by a crocodile and he chewed the bark and put it on his wound,” Professor Quinn said.

“It was unclear whether the benefit came from chewing the plant or using it as a poultice on the wound.

“Our research has since isolated a number of compounds from the plant's bark and tested them for analgesic properties. Several compounds have shown encouraging signs in pre-clinical testing.”

Griffith University and the Jarlmadangah Aboriginal Community have taken out patent applications for the compounds.
Avexis Director Mr Andrew Loch said the company planned to develop products for natural remedy and pharmaceutical markets based on the licensed technology.

"There's an unmet need in the management of pain, so there's a significant global market opportunity," Mr Loch said.

The Jarlmadangah Burru Aboriginal Community Project Coordinator Mr Paul Marshall said this new biotech venture was possibly a first for Australia.

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“The Indigenous community initiated the research partnership with Griffith and it is notable that the University embraced the community as equal partners in the project,” Mr Marshall said.

Jarlmadangah Burru Community Chairman Mr William Watson said his people looked forward to the day when this traditional medicine was available around the world to help people suffering from pain.

"This medicine has been used by our people for many generations and the thought that it could soon be improving the lives of millions of people around the world fills us with pride," Mr Watson said.

A formal signing ceremony has taken place at the remote Aboriginal community area, east of Broome, with representatives from Griffith and Avexis.
Ends


Contacts

  • Professor Ron Quinn, Executive Director of the Eskitis Institute  (07) 3735 6006
  • Nicholas Mathiou, Director Griffith Enterprise 0419 659 714
  • Paul Marshall, Project Coordinator for Jarlmadangah Burru Aboriginal Community  0408 925725
  • Andrew Loch, Director Avexis Pty Ltd 0407 960 004


Researchers find chink in the armour of viral 'tummy bug'

Researchers at Griffith University's Institute for Glycomics in collaboration with colleagues at the University of Melbourne have moved a step closer to identifying a broad spectrum treatment for the dreaded 'viral tummy bug' or rotavirus.

These highly-infectious viruses are the leading cause of severe diarrhoea in young children, responsible for thousands of hospitalisations in the developed world, and hundreds of thousands of deaths each year in developing countries.

Institute Executive Director Professor Mark von Itzstein said research findings published in the world-leading Chemical Biology journal Nature Chemical Biology this week demanded a total rethink of how these viruses work.

"Rotaviruses are thought to infect the bodies by sticking to certain types of sugars called sialic acids on the surface of our stomach cells. They then enter cells and reproduce rapidly, causing illness," he said.

"Rotavirus vaccines are still in their infancy, as problems emerged with the first vaccine that was trialled a number of years ago. While other vaccines are now in clinical use, new directions are required in the development of potential drugs to prevent or treat this deadly virus."

He said that to better understand how carbohydrates are involved in rotavirus infection, researchers had focussed on treating mammalian cells with a protein called sialidase which cuts these surface sugars so the virus cannot attach.

Previous to his group’s work most scientists believed only some of the many strains of rotavirus infection could be prevented with sialidase treatment while others were apparently immune to its effects.

This led to the conclusion that some viruses depend on sialic acid to infect the body while others were thought to cause infection independent of sialic acid.

"Unsuccessful attempts to reduce rotavirus infection with this treatment led scientists to group rotaviruses into two classes: ‘sialidase-sensitive’ and ‘sialidase-insensitive’ strains," he said.

The team used nuclear magnetic resonance spectroscopy, 3D modelling and cell-based assays to observe the interaction between the virus and host cells.

"We found that a human strain previously through insensitive to sialidase does in fact recognise and bind to sialic acid, but it is a sialic acid not accessible to sialidase treatment." Professor von Itzstein said.

"This reveals that there is a common chink in the armour of these rotaviruses.

"This discovery is the first step in designing a broad-spectrum drug able to exploit this weakness to combat many types of human and animal rotaviruses. "


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