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.
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.
Demystifying The Burden Of Intensive Care Survivorship - Understanding Muscle Wasting And Falls
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
For individuals who survive an intensive care admission, there is no prevention or cure for the development of intensive care acquired weakness. This project aims to examine the impact of muscle loss and weakness on balance, falls and the ability to walk. These outcomes are important to patients as it directly impacts on the ability to undertake day-to-day activities, their confidence and return to work. Results will be used to inform clinical practice and improvement in patient care.
The Role Of The Systemic Milieu In Preventing Motor Unit Remodelling And Loss During Ageing
Funder
National Health and Medical Research Council
Summary
Motor unit remodeling and loss contributes to the decline in muscle mass, strength and quality of life in our aging population. Recent data shows that exposing aged mice to 'blood-borne factors' from the circulation of a young mouse can reverse the age-associated deficits in motor unit structure and function. A better understanding of the factors controlling these anti-aging effects will be vital for finding new compounds to reverse the aging process and improve quality of life.
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.
Determining The Pathomechanics Of Muscle Weakness In Older Individuals With Toe Deformities In Order To Develop Evidence-based Intervention Strategies To Restore Foot Function
Funder
National Health and Medical Research Council
Funding Amount
$316,251.00
Summary
Hallux valgus and lesser toe deformities are highly prevalent foot problems in older people that can cause foot disfigurement, physical discomfort, and increase the risk of falling. This study will investigate how toe muscle weakness is affected by these toe deformities as the basis upon which to develop interventions that can restore foot function in older individuals, in order to reduce falls risk, foot pain and, in turn, improve independence and quality of life throughout ageing.
Mechanisms Regulating Excitation-contraction Coupling In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$687,750.00
Summary
Muscle contraction occurs when an electrical impulse from a nerve travels over the surface of a skeletal muscle fibre and triggers the release of calcium ions from special stores inside the fibre. However, little is known about the regulatory mechanisms involved in turning on and turning off the calcium release. This project investigates the properties of the calcium release and what processes are involved in regulating it. Information about this is vital for understanding how normal muscle work ....Muscle contraction occurs when an electrical impulse from a nerve travels over the surface of a skeletal muscle fibre and triggers the release of calcium ions from special stores inside the fibre. However, little is known about the regulatory mechanisms involved in turning on and turning off the calcium release. This project investigates the properties of the calcium release and what processes are involved in regulating it. Information about this is vital for understanding how normal muscle works and why muscles show reduced performance with exercise (muscle fatigue), with aging, and in certain diseases.Read moreRead less
An Early Intervention To Prevent Muscle Weakness In Intensive Care
Funder
National Health and Medical Research Council
Funding Amount
$82,607.00
Summary
Patients commonly suffer from a debilitating and globally pronounced weakness post intensive care admission. The causes and ways to prevent this weakness are not fully understood. This study will investigate the benefits of early exercise involving electrical stimulation of the leg muscles during in-bed cycling and will compare changes in muscle size and strength compared to usual care. We will also examine why muscles become weak so quickly, to help target future treatments to prevent weakness.
Role Of Nitric Oxide And Reactive Oxygen Species In Excitation-contraction Coupling In Skeletal Muscle.
Funder
National Health and Medical Research Council
Funding Amount
$163,250.00
Summary
Excitation-contraction (E-C) coupling is a term used to broadly describe the sequence of cellular events that starts with an electrical signal at the surface membrane of a muscle cell and which then ultimately leads to muscle contraction. Although the overall sequence is known, there remain many gaps in our understanding of the mechanisms involved not only related to normal muscle function but to how this function may be impaired by excessive exercise and disease. Many cellular metabolites contr ....Excitation-contraction (E-C) coupling is a term used to broadly describe the sequence of cellular events that starts with an electrical signal at the surface membrane of a muscle cell and which then ultimately leads to muscle contraction. Although the overall sequence is known, there remain many gaps in our understanding of the mechanisms involved not only related to normal muscle function but to how this function may be impaired by excessive exercise and disease. Many cellular metabolites contribute towards the normal control of muscle contraction, while others contribute to its impairment. Reactive oxygen species (ROS), which includes nitric oxide (NO) and related molecules, are metabolic factors often referred to as cellular oxidants. They are thought to have an essential role in controlling normal muscle function. Paradoxically, they are also implicated in the impairment of muscle function associated with fatigue, disease and aging. How these molecules both control normal muscle activity and also contribute to impairment of such function remains unclear. Thus, the central aim of this project is to identify the mechanisms by which the cellular oxidants, NO and other ROS, both control normal E-C coupling in skeletal muscle fibres and how they contribute to muscle fatigue. Clearly, understanding how skeletal muscle normally contracts is essential in order to better understand how muscle function can become impaired with exercise, disease and age. The work from this study will provide insight into both normal muscle physiology and how muscles fatigue and ultimately provide new methodologies and drugs that may combat fatigue, disease and age related changes to muscle function.Read moreRead less