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.
This project will examine Activins, as contributing factors to the loss of lean and fat mass that is commonly observed in patients with advanced cancer, and evaluate the therapeutic prospects of administering novel engineered Activin inhibitors, to prevent Activin-induced disease.
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.
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 Anorexia/cachexia: Mechanisms For Anorexia And Appetite Regulation By Tumour Derived MIC-1/GDF15
Funder
National Health and Medical Research Council
Funding Amount
$643,060.00
Summary
We have recently discovered that MIC-1 is a new appetite suppressive agent which when overproduced in some diseases like cancer, causes severe weight loss. This project sets out to determine the mechanisms it employs in regulation of appetite centres in the brain.