Foundation Director Professor Ronald Quinn is pursuing a cure for Tuberculosis (TB), and has had some encouraging early results.
TB is one of the top 10 causes of death worldwide. In 2015, 10.4 million people fell ill with TB and 1.8 million died from the disease (World Health Organisation). Drug resistance has also been a major issue for those trying to help sufferers.
Professor Quinn and his team are building a pipeline partly based on High Throughput Screening (HTS) undertaken by the AstraZeneca Company. They tested the Institute’s large NatureBank library of fractions from plants and marine invertebrates on a highly virulent pathogenic strain of TB. They found several hundred active fractions that had an impact on the TB strain. (Fractions are a partially purified mixture of natural products.)
A second input to the pipeline uses the technology of fragment-based drug discovery. Using this approach the Quinn team has identified pure compounds, which, when joined together synthetically, may be developed to produce a drug to combat TB.
The findings fit into the pipeline which aims to translate fundamental lab research into the clinical setting – where candidate drugs are tested on humans; and eventually, if all goes well, developed into a commercial product. Because of the inherent possibilities of this research, the early findings have not yet been published.
Malaria is one of the world’s most significant infectious diseases, resulting in a child dying every two to three minutes. This means that more than 1,000 children die of malaria every day.
Researchers at GRIDD are playing a key role in the fight to eradicate malaria, including Professor Kathy Andrews’ (s1) team of biomedical scientists who are working to identify new drugs to prevent and treat this major parasitic disease.
Kathy and her team work with national and international collaborators to identify weaknesses in the malaria parasite and then exploit those weaknesses to develop new malaria drug candidates that may help to combat drug resistance and eradicate malaria.
The impact of malaria
As a young scientist, Kathy visited sub-Saharan Africa and saw the devastating effects of malaria first hand. This experience continues to inspire her to play her part in solving the global puzzle of how to prevent, treat and ultimately eradicate malaria.
The World Health Organisation (WHO) explains that malaria is caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. In 2015, 95 countries and territories had ongoing malaria transmission; equating to around 3.2 billion people – or almost half of the world’s population.
There is some good news. Between 2000 and 2015, the WHO reports that the number of cases of malaria fell by 37% globally. In that same period, malaria death rates fell by 60% globally among all age groups and by 65% among children under five[s2] . http://www.who.int/malaria/media/world-malaria-report-2015/en/
New drugs for malaria are urgently needed
Currently malaria prevention and treatment rely on antimalarial drugs and public health measures, including vector control using insecticide-treated mosquito nets and indoor residual spraying. A broadly effective vaccine is not yet available and while current treatment drugs are effective, malaria parasite drug resistance is a major issue that threatens recent reductions in malaria cases and deaths. Drugs to prevent malaria from occurring are limited.
A major goal of the Andrews team is to work towards developing effective new drugs to prevent malaria. Drugs to prevent malaria need to be different from those used for malaria treatment and the Andrews team is focusing on agents that can kill malaria parasites differently (for example more slowly) than treatment drugs. This approach is important as it will limit the possibility of a new preventative drug from failing due to resistance to treatment drugs.
Working with collaborators that include Australia’s Commonwealth Scientific and Industrial Research Organisation (CSIRO) and the world’s leading not-for-profit malaria drug development organisation, the Medicines for Malaria Venture, the Andrews team is currently funded by grants from the Australian National Health and Medical Research Council (NHMRC).
Kathy is a ‘Griffith graduate through and through’ having completed her undergraduate, honours and PhD studies in Microbiology at the university before working overseas in Germany and other institutes in Australia for over a decade. She was delighted to return to Griffith in 2012.
“Here at Griffith University and the Institute, we’re making an important contribution to infectious diseases’ research both locally and on the world stage. I want to continue to be part of that vital work. I want us to be the best, to be remarkable, so that we can positively impact the lives of people suffering from malaria and other major infectious diseases,” said Kathy.
Infectious and Neglected Tropical Diseases:
Malaria, Chagas disease, Leishmania and Human African Trypanosomiasis
Impact of malaria and neglected tropical diseases
Neglected tropical diseases (NTDs) and malaria belong to a diverse group of primarily parasitic diseases which occur in tropical and subtropical regions throughout the world. These diseases affect more than 1 billion people, and impact on developing economies to the tune of millions of dollars every year (WHO 2015 Report).
Collectively, neglected tropical diseases (NTD), and malaria, result in the deaths of several million people every year. Malaria alone is responsible for almost 500,000 deaths per annum. The impact of NTDs is felt by millions more people through the debilitating short and long term effects they have on both individuals and their communities.
Current therapeutics have limited effects across all stages of these diseases and many have severe side effects, some life threatening. Those drugs that are effective are also at risk of resistance development, posing the threat that they will lose their efficacy in the future.
Professor Vicky Avery, a distinguished scholar who has worked extensively in the pharmaceutical industry, is optimistic about her team’s efforts. Her lab is tackling these problems on a number of different fronts to improve our understanding of NTD biology and to discover new drugs to treat NTDs.
Many parasites investigated by the Avery lab have both human and insect (vector) hosts. It is essential that the complete life cycle of each parasite can be replicated in the lab and that the parasite retains infectivity when used experimentally. Thus, two critical limiting factors for NTD drug discovery, prior to testing compounds, is the establishment of highly reproducible culturing systems and production of large quantities of the different parasite stages for screening purposes. The Avery lab has succeeded in overcoming these limiting factors for all the parasites they are working on.
Innovative technologies and strengths
The Avery lab provides the key chemical starting points for the drug discovery and development pipeline. From concept, through to pre-clinical drug development, the team provide sophisticated assays with ever increasing complexity and functionality, using the most advanced high throughput and high content imaging systems available for drug discovery in Australia.
An essential component of their research is ensuring that the discovery platforms accurately reflect and where possible, mimic, the in vivo situation. This increases the likelihood of finding compounds which will translate in vivo and work effectively in people. The comprehensive imaging platforms span multiple life-cycle and developmental stages of the parasites, and so are highly informative.
Utilising High Throughput Screening (HTS) to determine how effective a compound is at killing the parasites, the Avery lab rapidly and reproducibly evaluate many 100,000s of compounds in a very short timeframe. Their capabilities and industry-based approach has provided the foundation for numerous long term and fruitful collaborations throughout the world.
Successful drug discovery requires commitment and a highly collaborative and cross-disciplinary environment.
The Avery lab has contributed significantly to NTD drug discovery over the past 10 years. They designed the first HTS assay to identify compounds which inhibit growth of the parasites causing Human African Trypanosomiasis (sleeping sickness).
Vicky’s team were the recipients of the Medicines for Malaria venture (MMV) MMV International Drug Discovery Project of the Year 2007 for innovative use of technology to identify new anti-malarials, and again in 2013 for their contribution to the clinical candidate, MMV390048. Many of the compounds they have identified or profiled during development have now progressed to clinical trials.
Vicky is passionate about this research. “I speak for my entire team when I say it is a great feeling to know we are making a difference. Our research has the potential to have a significant impact and help some of the world’s poorest people overcome devastating diseases.”
Professor Avery continues to work in collaboration with the Medicines for Malaria venture (MMV); Drugs for Neglected Diseases initiative (DNDi), and more recently with the Global Health Initiative (GHIT Fund - Japan).