Developing Synergisers Of The Antimalarial Drug, Chloroquine, For The Treatment Of Chloroquine-resistant P. Falciparum.
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
Malaria is a debilitating parasitic disease that is responsible for the deaths of about two million children each year. As drugs, such as chloroquine, become increasingly useless due to the development of parasite resistance, there is an urgent need to understand the mode of action of and the molecular basis of resistance to existing antimalarials and to design affordable treatments that can replace chloroquine. It is known that some compounds, that have only poor antimalarial activity themselve ....Malaria is a debilitating parasitic disease that is responsible for the deaths of about two million children each year. As drugs, such as chloroquine, become increasingly useless due to the development of parasite resistance, there is an urgent need to understand the mode of action of and the molecular basis of resistance to existing antimalarials and to design affordable treatments that can replace chloroquine. It is known that some compounds, that have only poor antimalarial activity themselves, can synergise the action of chloroquine. This may involve the inhibition of the activity of proteins that directly or indirectly extrude chloroquine from its site of action in the parasite's digestive apparatus. Unfortunately, thechloroquine synergisers examined to date have been too toxic to be useful in vivo. In preliminary studies we have identified some compounds that would be suitable for use in malaria patients, including a widely used antimalarial drug, primaquine, that can synergise the activity of chloroquine against chloroquine-resistant parasites. We will attempt to understand the molecular basis of this interaction. This will allow us to define optimal combinations of chloroquine and a resistance-reversing quinoline for use treating malaria. This could extend the clinical life of this important antimalarial drug. The information obtained may also help to design novel antimalarial drugs.Read moreRead less
Combating Giardiasis By Investigating New Potent Compound Series As Leads For Improved Treatment Options
Funder
National Health and Medical Research Council
Funding Amount
$776,028.00
Summary
Giardia parasites infect ~1 billion people globally and are responsible for significant morbidity and disadvantage. There is no licensed vaccine and current treatment options are inadequate, resulting in poor compliance, treatment failures, rapid re-infection and drug resistance. New therapies are needed to combat this parasite and improve the health of millions world-wide. We will address this issue by investigating new drug candidates for the treatment of Giardia infections.
In 2013 there were ~200 million clinical cases of malaria, causing ~600,000 deaths. All antimalarial drugs are now associated with malaria parasite resistance. Thus, new therapies are urgently needed, including new drugs to prevent this disease. We have made the exciting discovery that an existing antimalarial drug can kill malaria parasites in a unique, previously unknown, manner. Here, we will investigate how this occurs and develop new drug candidates for malaria prevention.
The WHO estimates there were ~189 million clinical cases & 584,000 malaria-related deaths in 2013. This translates to ~1,600 child deaths daily. There is no licensed malaria vaccine & all available drugs are associated with resistant parasites. This enormous health issue is driving the search for new therapies. We address this issue by identifying new drug candidates for malaria prevention, with unique modes of action to treatment drugs in order to overcome issues of parasite drug resistance.
New Antimalarial Drug Leads Targeting Multiple Species And Life Cycle Stages
Funder
National Health and Medical Research Council
Funding Amount
$818,477.00
Summary
Malaria causes ~200 million clinical cases and >430,000 deaths annually. Prevention and treatment relies on drugs, however malaria parasite drug resistance is an enormous problem. To address this issue, and aim towards eliminating malaria, we need to develop new drugs. This project addresses this important health need by investigating the ability of new chemical compounds, developed at CSIRO, to kill human-infecting malaria parasites during different parts of their complicated lifecycles.
Metabolomic Analysis Of Plasmodum Falciparum And Mode Of Action Of Antimalarial Compounds
Funder
National Health and Medical Research Council
Funding Amount
$917,196.00
Summary
There is an urgent need to develop new drugs to treat malaria, one of the most important diseases to afflict humanity. We have developed new analytical approaches for measuring parasite metabolism while they live inside host cells. These approaches will be used to identify metabolic pathways that are essential for parasite infectivity and to understand the mode of action of new classes of antimalarial compounds
Investigating The Therapeutic Potential Of FTY720 For Human African Trypanosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$653,736.00
Summary
FTY720, is a drug currently used to treat multiple sclerosis, which we have shown is also be able to kill the parasite responsible for African sleeping sickness, Trypanosomes. We aim to identify the target the drug acts on in the parasite to have its affect. Our objective is to improve the activity further by chemical modification to produce a potent, orally available and well characterised, non-toxic drug suitable for preclinical development.
Application Of New Chemistry Approaches For Antimalarial Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$74,263.00
Summary
Malaria kills approximately one million people annually. Currently there no vaccine and many of the available drugs are becoming less effective due the resistance of this highly adaptable parasite. My aim is to develop new chemical classes of drugs that inhibit different targets in the malaria parasite to the currently available drugs. In addition to this I aim to improve the present systems for assessing antimalarial drug effects using new chemical approaches and live parasite assays.
Identifying Metabolic Pathways In Leishmania Parasites And Their Host Cells Required For Virulence
Funder
National Health and Medical Research Council
Funding Amount
$989,110.00
Summary
Our lack of understanding of microbial metabolism in infected animal tissues has hindered the development of effective therapies. This is particularly true for many parasitic diseases, including Leishmania spp that cause devastating disease throughout the tropics. We will utilize a range of innovative analytical and genetic approaches to identify metabolic pathway in Leishmania parasites and infected host cells that are required for virulence and are potential drug targets.
Parasitic infections are a significant global health problem, resulting in more than a million deaths annually. Unfortunately there is no licensed vaccine available for any human parasitic infection, and in many cases current drugs suffer from issues of parasite drug resistance. To address this problem this project brings together leading researchers from the European Union, Brazil, and Australia to discover and develop new types of drugs for four major human parasitic diseases: schistosomiasis, ....Parasitic infections are a significant global health problem, resulting in more than a million deaths annually. Unfortunately there is no licensed vaccine available for any human parasitic infection, and in many cases current drugs suffer from issues of parasite drug resistance. To address this problem this project brings together leading researchers from the European Union, Brazil, and Australia to discover and develop new types of drugs for four major human parasitic diseases: schistosomiasis, leishmaniasis, Chagas disease and malaria.Read moreRead less