Establishing STARS As A Therapeutic Target To Reduce Muscle Wasting And Improve Muscle Function
Funder
National Health and Medical Research Council
Funding Amount
$446,189.00
Summary
Muscle wasting occurs rapidly with disuse after injuries occurring at work, during sport, with chronic disease and in road accidents. It is also a consequence of ageing. Muscle wasting and reduced muscle function places considerable financial strain on our health care system. We aim to use gene therapy and pharmacological interventions to increase the levels of a protein called STARS. We hypothesize that STARS will reduce disuse-induced muscle wasting, increase recovery and improve function.
Therapeutic Potential Of Skeletal Muscle Plasticity And Slow Muscle Programming For Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$780,476.00
Summary
There is no cure for DMD, a devastating, life-limiting muscle disease causing progressive muscle wasting in boys and young men. A potential therapy may come from modulating muscle activity patterns to promote a protective slow muscle phenotype through low-frequency stimulation protocols and/or well-described pharmacological ‘exercise mimetics’. This proposal will evaluate their therapeutic merit in mouse models of DMD to answer the key questions to advance this approach to the clinic.
Rescuing The Dystrophin-glycoprotein Complex To Protect Muscles From Wasting Conditions
Funder
National Health and Medical Research Council
Funding Amount
$833,340.00
Summary
Existing medical strategies to counteract severe muscle wasting disorders are compromised because of dysfunctional signalling around a cluster of proteins called the dystrophin-glycoprotein complex (DGC) located at the muscle membrane. To address this significant unmet medical need, this proposal investigates novel approaches to retain or restore DGC integrity at the muscle membrane with the goals of preserving and protecting muscles during serious wasting conditions.
Cancer cachexia is a devastating disease characterised by muscle wasting, weakness and fatigue. It impairs patient quality of life and accounts for >20% of cancer-related deaths. This project will identify factors responsible for cancer cachexia and develop new strategies to alleviate wasting and weakness in cancer patients, to improve their quality of life and reduce mortality.
Therapeutic Potential Of Modulating Heat Shock Protein Expression For Muscle Wasting Disorder
Funder
National Health and Medical Research Council
Funding Amount
$1,172,146.00
Summary
Heat shock proteins help stressed proteins fold back to their original conformation and restore function. In a discovery published in Nature we identified induction of heat shock protein 72 (Hsp72) as a novel approach for muscular dystrophy and other conditions where there is inflammation and muscle weakness. This proposal will investigate whether Hsp72 induction is similarly effective in tackling the muscle wasting and weakness in conditions like ageing and frailty and in muscle injury.
Roles Of Vitamin D In Skeletal Muscle And Satellite Cells
Funder
National Health and Medical Research Council
Funding Amount
$380,891.00
Summary
Vitamin D deficiency leads to muscle pain and weakness that are reversible with vitamin D supplementation. However, precise biological effects of vitamin D in skeletal muscle are unclear. In this fellowship, novel mouse models and innovative techniques will be used to examine vitamin D signalling pathways in whole muscle and muscle stem cells. Ultimately, the therapeutic potential of the vitamin D pathway in treatment of muscle disorders and age-related muscle wasting will be explored.
An Essential Role For Skeletal Muscle FoxO1 In Protecting Against Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$593,888.00
Summary
Skeletal muscle is the largest organ in the human body and accounts for approximately 80% of glucose disposal after a meal. We have identified a transcription factor, namely FoxO1, that appears protect against obesity-induced insulin resistance by promoting energy consumption. This project will examine whether skeletal muscle specific activation of FoxO1 is a possible therapeutic target for the treatment of obesity-induced insulin resistance.
Targeting A Novel Long Non-coding RNA That Is Dysregulated In Skeletal And Cardiac Muscle Disease
Funder
National Health and Medical Research Council
Funding Amount
$621,557.00
Summary
Recently, evidence suggests that cellular pathways that promote disease in skeletal and cardiac muscle, may be significantly influenced by a new class of molecules known as lncRNAs. Indeed a handful of studies have shown that therapies which target lncRNAs, can reduce disease severity. Thus, the identification of new lncRNAs that influence muscle health may present new therapeutic options to treat muscle diseases, where very few treatments currently exist. Here, we describe one such lncRNA.
Reprogramming Macrophage Function In The Elderly To Rescue Impaired Inflammatory Responses To Muscle Injury
Funder
National Health and Medical Research Council
Funding Amount
$410,983.00
Summary
Muscle injury in the elderly often takes longer to heal than in younger people, however the cells responsible for this delayed healing are not well understood. Key inflammatory cells required for muscle repair in young hosts are macrophages. However, during aging we have shown that macrophage function is altered, but the mechanism is unknown. This project aims to determine the mechanisms behind age-related changes to macrophages and whether they can be targeted to improve elderly muscle repair.
Exploring The Therapeutic Potential Of TRAIL In Diabetes And The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$446,374.00
Summary
TNF-related apoptosis-inducing ligand (TRAIL) is a protein with potentially useful actions in human health and disease. TRAIL is able to prevent atherosclerosis, the cause of heart attacks and strokes. In addition, we have recently shown that its actions on fat and the pancreas may prevent the development of the metabolic syndrome and type 2 diabetes. These studies will explore the therapeutic potential of TRAIL for the prevention of diabetes and heart disease in a range of animal models.