Epilepsy is one of the most common chronic neurological disorders; it affects 1% of the world’s population, yet about 1 in 3 patients fail to achieve seizure control with current drugs. We will improve the properties of small molecules (drugs) that specifically target the GTPase activity of the enzyme dynamin, to reduce seizure effect in the brain by a novel mechanism. We will optimize and pre-clinically test these future chemical entities as potential anti-epileptic drugs.
We aim to develop a new class of cholesterol-lowering drugs by blocking the interaction between a protein in the blood called PCSK9 and its receptor, which is implicated in cholesterol absorption. We will do this by designing small stable peptides (mini proteins) that mimic part of the receptor and have the potential to interfere with the normal PCSK9 binding process. These drugs should be less expensive and potentially less immunogenic than competing therapies based on antibodies.
Further Development Of The Clinical Potential Of H2 Relaxin
Funder
National Health and Medical Research Council
Funding Amount
$651,768.00
Summary
The hormone relaxin mediates cardiovascular and kidney changes during pregnancy. These important functions have led to its current use in clinical trials for the treatment of acute heart failure, a condition affecting millions of patients worldwide. However, there is an urgent need for a longer lasting form of relaxin for prolonged treatment of patients. Our studies will focus on understanding the blood breakdown of the peptide to lead to the design of longer lasting relaxin analogues.
Chronic pain is a significant global health, economic and social problem, with the annual economic burden estimated at approximately $40 billion in Australia. My research will focus on the discovery and structure-function of venom peptides (trivially called toxins) from cone snails and spiders plus other Australian venomous creatures that modulate sodium and calcium channels in peripheral pain and associated pathways and optimise these for clinical development.
Peptide Conjugates Of Splice-correcting Oligonucleotides For Enhanced In Vitro And In Vivo Delivery For Neuromuscular Disease Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$332,347.00
Summary
Currently, there is no known cure for certain neuromuscular genetic disorders. However, recently identified synthetic DNA-type biomolecules have shown promising results in reversing such diseases in mice. These biomolecules cannot easily enter the cells in high enough quantity to elicit their beneficial effects. Therefore, this project will aim at identifying novel vecotrs that, when coupled to these biomolecules, are capable of delivering them into specific cell types as well as into the brain.
Evaluation Of Novel Pyrrolo/Iminoquinone Antimalarial Compounds
Funder
National Health and Medical Research Council
Funding Amount
$614,250.00
Summary
The development of new antimalarial drugs is an unmet global health priority. In this project we will investigate novel compounds that have been found to display promising in vitro antimalarial activity. We will modify these compounds to make them more drug-like, and assess their efficacy in vivo using malaria animal models. These studies have the potential to identify compounds that may result in a new therapy for malaria, the worlds' most significant tropical infectious disease.
Next Generation Relaxin Molecular Probes And Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
The peptide hormone relaxin is poised to be the first new treatment for acute heart failure in more than 40 years. However, like other therapeutic peptides, it has a very short duration of action due to its rapid clearance by the body. My work will utilize powerful medicinal chemistry methods to develop new analogues of relaxin that have much longer action by complexing it with sugar or making relaxin polymers. I will also produce smaller relaxin analogues that will be cheaper to manufacture.