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.
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.
This research draws together my expertise in medicinal chemistry, biochemistry, pharmacology and virology to design and develop new compounds that we can use to interrogate and regulate human and viral proteins that cause disease. Protein, cell and animal studies relevant to major 21st century health burdens (such as inflammatory, infectious and metabolic diseases, cancer, pain and viral infections) will provide important new information on mechanisms of disease development and drug action.
Unraveling Fibrosis By Pharmacological Targeting Of The G Protein-coupled Receptor, RXFP1
Funder
National Health and Medical Research Council
Funding Amount
$798,618.00
Summary
Peptides, with their high specificity and low toxicity profiles, are highly attractive alternatives to small molecule drugs. H2 relaxin, a peptide hormone, has a strong potential for treating fibrosis. However, the large size of H2 relaxin makes it difficult and expensive to manufacture. Once administered to patients, it is also quickly degraded. We have developed a small anti-fibrotic relaxin peptide, and propose to understand its mechanism of action and improve its therapeutic indices.
Venoms To Drugs: Translating Venom Peptides Into Human Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Many disorders of the nervous system, including chronic pain, epilepsy and the neuronal degeneration suffered following a stroke, result from malfunction of channels that ferry ions across neuronal cell membranes. There are very few drugs available for treating these disorders and they often have debilitating side-effects. We are developing potent and selective modulators of these ion channels as the next-generation of safe and effective analgesic, anti-epileptic, and neuroprotective drugs.
Modulation Of Feeding Through Pharmacological Targeting Of The Relaxin-3 Receptor RXFP3
Funder
National Health and Medical Research Council
Funding Amount
$584,955.00
Summary
Relaxin-3 is a neuropeptide that regulates a number of physiological processes, including food intake, suggesting that the relaxin-3 receptor RXFP3 may be a new target for treatment of eating disorders such as obesity. This project will develop new selective and high-affinity ligands for RXFP3, which will be critical pharmacological tools for the preclinical studies and evaluation of this system.
Understanding The Structure/function Relationships Of The Iron Regulatory Peptide Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$365,126.00
Summary
This project seeks to understand the interactions between the peptide hormone hepcidin and its receptor and use this information to develop new drugs. Hepcidin is the major iron-regulatory hormone in humans and a range of iron-related diseases are caused by incorrect levels of this hormone. Many Australians are affected by these diseases so the development of hepcidin-based treatments has the potential to have significant impact on the overall health of the community.
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.
Developing Subtype-selective Blockers Of Acid-sensing Ion Channels For Treating Peripheral Pain
Funder
National Health and Medical Research Council
Funding Amount
$641,407.00
Summary
Chronic pain is a huge medical problem that affects 1 in 5 adults. There are few drugs available for treating chronic pain, and many of these have limited efficacy and dose-limiting side-effects. Acid-sensing ion channels are proteins that play an essential role in the specialised nerves that sense pain signals. The ultimate goal of this project is to engineer highly selective blockers of these channels that can be used to develop effective analgesics for treating patients with chronic pain.
Expanding The Repertoire Of Immunomodulatory Drugs: Targeting The Melanocortin System Using Engineered Cyclic Peptides
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Autoimmune diseases, including rheumatoid arthritis and psoriasis, have profound impacts on the lives of many Australians. New drugs are required for these diseases as existing treatments are expensive, become less effective with repeated use or cause adverse side effects. My project will work towards addressing this need by investigating the potential of ultrastable cyclic miniproteins as scaffolds for displaying bioactive peptides that are known to restore immune self-tolerance.