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GHIT Fund boosts anti-malarial drug research at Griffith University

Eskitis Institute tackles Plasmodium falciparum and Plasmodium vivax in bid for medicine that treats disease, combats resistance and prevents relapse

Griffith University

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IMAGE: This is Professor Vicky Avery, from Griffith University's Eskitis Institute for Drug Discovery. view more

Credit: Griffith University

Griffith University's contribution to the international fight against malaria has received a major boost from Japan's Global Health Innovative Technology Fund.

Following an investment of $US637,000, a research team from Griffith's Eskitis Institute for Drug Discovery (Queensland, Australia) led by Professor Vicky Avery -- along with partners from Japanese pharmaceutical firm Daiichi Sankyo, the Swiss-based Medicines for Malaria Venture, Monash University and the University of California-San Diego -- can continue advances towards more effective anti-malarial drugs.

Professor Avery says the ultimate aim is to develop a medicine that treats malaria caused by Plasmodium falciparum and Plasmodium vivax, combats drug resistance and, ideally, prevents relapse associated with parasite dormancy.

As well as treating patients, researchers are focusing on ways to protect people from being infected and, critically, of blocking transmission of the parasite to the mosquito host. Attacking the parasite at multiple stages of the life cycle is necessary to achieve the goal of malaria eradication.

"This new project extends our ongoing long-term collaboration with MMV and the more recent one with GHIT, which has been responsible for identifying new chemical entities for progression through the drug discovery pipeline," says Professor Avery.

"Our involvement has been as a result of the high quality drug discovery efforts in malaria undertaken in my laboratory.

"The assays developed to undertake the screening and biological profiling of compounds in search of new leads are based on state of the art image-based technologies.

"We have proven that within an academic environment we can undertake drug discovery at industry standards. Indeed, we are equipped with systems which usually would only be found within large Pharma."

Launched in 2013 with an initial commitment of more than $US100 million, the GHIT Fund is a public-private partnership between six Japanese pharmaceutical companies, the Japanese Government and the Bill & Melinda Gates Foundation.

The latest announcement marks GHIT's second round of funding to support very early-stage drug research through its "Hit-to-Lead Platform".

This initiative invests in projects with the goal of converting drug "hits" from compound libraries into "lead compounds" that show promise against infectious diseases, but require further research and development before testing as human drugs.

In the first phase, GHIT invested in Professor Avery's team to undertake the screening of 50,000 compounds from Daiichi Sankyo, which identified several "hit" series able to inhibit the malaria parasite growth.

According to the World Health Organisation, the global malaria death rate decreased by 47 per cent from 2000-13. However, challenges such as inevitable resistance to malaria drugs continue to pose a serious threat.

"The drug discovery efforts within the Eskitis Institute are well recognised globally, which is highlighted by our extensive collaborations and high quality publications," says Professor Avery.

For example, late last year Professor Avery co-authored a paper published in the journal Nature Communications that revealed the promise of a new chemical class of molecules.

Called pyrazoleamides, they disrupt a molecular salt pump on the surface of malaria parasites. Blocking this pump causes the parasites to take up water, causing them to swell, burst and die.

A subsequent paper in PNAS identified another chemical class and indicated further progress in the mission to slow drug resistance and produce fast-acting anti-malarials.

"Drug discovery is a multidisciplinary process, hence being able to collaborate well with individuals from different disciplines is essential. I believe this is something we do well," says Professor Avery.

"I also believe that with the concerted and focused efforts that everyone is now taking in their drug discovery efforts, and the requirement that new drugs have activity against different stages of the parasite life cycle, including blocking transmission, we have a very good chance of providing a suite of new drugs to alleviate the current concerns with resistance."

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Papers: http://www.nature.com/ncomms/2014/141125/ncomms6521/full/ncomms6521.html and http://www.pnas.org/content/111/50/E5455.abstract?sid=b1dfcb0e-919c-4681-b6d2-1a3e576b8fe3

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