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.
Investigating Hippo Signalling As A Novel Cause Of Muscle Disease, And As A Target For New Interventions To Combat Frailty
Funder
National Health and Medical Research Council
Funding Amount
$460,509.00
Summary
We will explore the role of the Hippo signaling pathway in muscle development, repair and remodelling. We propose that this little-known pathway which affects organ development, is key for maintaining healthy muscles, and is affected in muscle wasting. Using gene therapy tools to alter this pathway in models of disease, we intend to clarify the role of Hippo signaling in muscle, and establish whether the pathway can be manipulated to treat physical frailty caused by muscle wasting.
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.
Clarifying Molecular Role Of IGF-1:Ea Isoforms In Skeletal Muscle Hypertrophy And Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$394,718.00
Summary
The growth factor IGF-1 is proposed as a therapeutic agent to increase muscle mass and to reduce muscle wasting resulting from denervation, disuse, ageing and dystrophy. Understanding the precise mechanisms of IGF-1 action is essential for the potential therapeutic use of this factor. This research is focused on the molecular role of IGF-1 in healthy muscle and in the conditions of muscle wasting and degeneration.
IGF-1 AS A THERAPEUTIC AGENT: HOW DOES IGF-1 AFFECT OXIDATIVE STRESS IN DYSTROPHIC AND AGED SKELETAL MUSCLE?
Funder
National Health and Medical Research Council
Funding Amount
$545,243.00
Summary
Loss of skeletal muscle mass (wasting) and function occurs in many clinical conditions, including muscular dystrophy, neuromuscular and inflammatory disorders, and also normal ageing. A growth factor (IGF-1) is a promising therapeutic as it increases protein synthesis. Muscle wasting (loss of protein) is also associated with increased oxidative stress. The project will evaluate the impact of IGF-1 on oxidative stress using genetically engineered mouse models of muscular dystrophy and ageing.
Molecular Mechanisms Of Wasting In Experimental COPD
Funder
National Health and Medical Research Council
Funding Amount
$389,521.00
Summary
Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Currently no therapies exist to halt the inevitable progression of the disease. To date most of the research has focused on the aspects of this disease which result in destruction of the lung however it is becoming incre ....Chronic obstructive pulmonary disease (COPD) is a major global health problem and has been predicted to become the third largest cause of death in the world by 2020. Cigarette smoking is the major cause of COPD and accounts for more than 95% of cases in industrialized countries. Currently no therapies exist to halt the inevitable progression of the disease. To date most of the research has focused on the aspects of this disease which result in destruction of the lung however it is becoming increasingly evident that COPD is a disease of multiple organs. Until recently it had been widely believed that the profound loss of exercise tolerance observed in COPD patients was due to impaired gas exchange secondary to lung structural damage. Loss of lean body mass (muscle) is now recognised as a major co-morbidity of COPD and a direct cause of functional impairment with patients suffering marked deteriorations in quality of life, increased mortality, breathlessness and decreased exercise tolerance. Skeletal muscle wasting is a powerful predictor of mortality in COPD, independent of the lung function impairment. Despite the clinical seriousness of muscle wasting and suggestive evidence that it may be reversible, little is known about the pathogenic mechanisms. Therefore the goal of this project is to use experimental models of COPD to identify the molecular basis of wasting, in order to restore skeletal muscle homeostasis. The insights gained from this research proposal may lead to the identification of potentially novel targets for the prevention and reversal of the debilitating and life threatening effects of skeletal muscle wasting in COPD. For the COPD patient this has the potential to increase quality of life, functional ability and life expectancy.Read moreRead less
The Effect Of Α-actinin 3 Deficiency On Regulation Of Skeletal Muscle Mass In Health And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$84,800.00
Summary
A common genetic variant results in absence of the fast muscle fibre protein ?-actinin-3 in more than one billion humans worldwide. Loss of ?-actinin-3 influences elite athletic performance, muscle bulk and strength in the general population, and disease severity in muscle wasting conditions. The goal of this study is to understand how ?-actinin-3 regulates muscle mass so that individuals at increased risk of muscle wasting may be identified and treated accordingly.
Using Gene Delivery Technologies To Define Novel Mechanisms Of Skeletal Muscle Adaptation, And Develop Muscle-directed Interventions For Frailty And Serious Illness
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
The focus of my research is to investigate the cellular mechanisms underlying regulation of skeletal muscle size and function in health and disease. By defining these processes we can establish the events contributing to muscle wasting and frailty commonly associated with serious illness and advancing age, and develop interventions to prevent/overcome this important contributor to poor health prospects and reduced survival.