Pain is a debilitating condition that affects the life of one in five Australians and has significant socioeconomic impact. Currently available pain killers often do not work, or have intolerable side effects including sedation and addiction. We have discovered a novel compound that avoids these side effects and provides effective analgesia as well as opioid-sparing effects in a number of relevant animal models. The aim of this project is to progress the compound towards clinical development.
Novel Analgesic Approaches: Harnessing Functional Interactions Between Sodium Channels And Opioids
Funder
National Health and Medical Research Council
Funding Amount
$329,076.00
Summary
Chronic pain is a debilitating condition that affects the life of one five Australians and has significant socioeconomic impact. Currently available pain killers often do not work, or have intolerable side effects. We have discovered that combination treatment with opioids and a novel venom-derived compound discovered by us provides effective pain relief. The aim of this project is to understand the mechanisms underlying this synergistic effect to develop new treatment approaches for pain.
Pain is one of the most frequent and costly health problems faced by Australia. Currently available painkillers often do not work, or have intolerable side effects. We thus need better approaches to treat pain. This project will define the role of the novel pain target Nav1.6 in clinically relevant pain states, including burns pain and chemotherapy-induced pain, with the aim to develop novel treatment approaches and painkillers for these difficult-to-treat conditions.
Identifying And Exploiting Novel Pharmacological Targets For Breast Cancer Treatment
Funder
National Health and Medical Research Council
Funding Amount
$442,214.00
Summary
Breast cancers are made up of different types of cancer cells, and not all cells contribute equally. A subset of cancer cells may be uniquely capable of driving tumor growth, rebuilding fatal tumors after therapy and establishing new tumors at distant sites. New therapies to inhibit the activity and survival of these cells will lead to better modes of treatment and greatly accelerate progress towards ending breast cancer.
Chronic inflammation underlies common and debilitating diseases and causes pain by unknown mechanisms. There is an urgent need to gain a deeper understanding of the mechanisms of chronic pain, which will allow the development of improved therapies with fewer side-effects. Our research program investigates the mechanisms of pain that are associated with inflammatory bowel disease and irritable bowel syndrome, with the goal of developing more effective and selective therapies.
Adenosine Receptor Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$682,163.00
Summary
Adenosine A1 receptor (A1R) activation confers powerful protection to heart cells, however clinical application remains suboptimal due to adverse effects such as a slowing in heart rate and decrease in blood pressure. Importantly a new class of compounds, A1R biased agonists, can mediate potent cardioprotection in the absence of adverse effects. This proposal will establish the molecular mechanisms involved and the scope to develop A1R biased agonists as a novel approach to treat heart disease.
Adenosine Receptor Context-Specific Biased Agonism To Treat Ischaemic Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,021,744.00
Summary
Heart attacks and secondary heart failure remain significant health burdens. Stimulation of adenosine receptors located on heart cells confers powerful cardiac protection, improving acute and longer-term heart function subsequent to a heart attack but avoiding the usual unwanted effects from this approach. We aim to better understand the mechanism of action of potential adenosine receptor therapeutics and establish the clinical potential of these compounds using animal models of heart failure.
Understanding Mechanisms Of Allostery And Biased Agonism At The Adenosine A1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$603,033.00
Summary
This project focuses on an important protein found in the heart. Drugs that activate this protein can protect the heart against damage that occurs after a heart attack, but they all have undesirable side effects. We have discovered a new class of molecule that can protect the heart without these side effects. We now seek to understand how these compounds work at the molecular level. This knowledge can facilitate the design of safer medicines for the treatment of cardiovascular disease.
Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is acti ....Understanding the mechanisms of class B GPCR-transducer coupling. Current effort in developing drugs targeting G protein-coupled receptors (GPCRs) often result in low success rate due to the lack of understanding of the complexity and the spatiotemporal control of receptor function. The research program aims to understand the molecular mechanisms of receptor/transducer selectivity. The proposal integrated multi-disciplinary approaches to provide a deeper understanding of how the receptor is activated responding to different ligands. The anticipated outcome including an enhanced capacity for understanding the fundamental biology, a stronger national and international collaborations. This will provide significant benefits including expanded basic knowledge and improvements in drug development efficiency. Read moreRead less
Molecular Characterisation Of The Glucagon-like Peptide 1 Receptor
Funder
National Health and Medical Research Council
Funding Amount
$681,953.00
Summary
The glucagon-like peptide 1 receptor is a major target for treatment of Type 2 diabetes and obesity. However, the development of drugs for this receptor is challenging due to limited understanding of potential sites of drug interaction and how individual drugs may differentially change signalling from the receptor. This project will address these critical knowledge gaps, which may allow for improved therapeutic outcomes.