Congenital Fibre Type Disproportion (CFTD): Disease Patterns And Pathogenesis Of Muscle Weakness
Funder
National Health and Medical Research Council
Funding Amount
$264,816.00
Summary
Congenital Fibre Type Disproportion (CFTD) is a type of genetic muscle disease that is caused by changes (mutations) in several different genes. Affected children usually have general muscle weakness from birth. We will compare medical findings and muscle MRI scans in different CFTD patients to develop guidelines for the care and diagnosis of CFTD patients. We will also study how gene mutations lead to weakness and the abnormalities seen on the muscle biopsy, focusing on the TPM3 gene.
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.
The Molecular Mechanisms Of Anabolic Androgen Actions In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in musc ....We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in muscle. We will study the growth of mouse muscle cells in culture, and measure their rate of growth when treated with androgens. All cells contain certain factors that control their growth and replication, and we will test whether androgens activate these factors to increase growth. We will also study the effect of androgens on muscle in mice, to investigate complex effects that only occur in real muscle. We will neuter male mice, which causes muscle wasting. Neutered mice will then be treated with androgens or placebo, and we will compare the muscle growth effect of androgen treatment versus placebo. We will measure muscle strength, size, and the number of muscle cells in treated and placebo mice. We will also see if the effects of androgen require a particular protein, the androgen receptor, which acts as a lock-key mechanism in cells, to allow them to respond to androgens. We will make a strain of mouse with a non-functional version of the androgen receptor only in muscle cells. This will determine if the muscle growth effects of androgens occur through a direct action on muscle, or indirectly through acting on other tissues in the body. This information will ultimately allow us to design more targeted androgen therapies for muscle wasting, that act only on muscle.Read moreRead less
The Effects Of ACTN3 R577X On Muscle Wasting And Repair, And Response To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$1,066,054.00
Summary
Complete loss of ACTN3 is normal and occurs in 1 in 5 people world-wide. While it does not cause disease, loss of ACTN3 results in ~10% reduction in muscle mass and strength. This has tremendous impact not only on the success of elite athletes but also the quality of life in people who are already frail. Precisely how ACTN3 affects muscle mass is unclear. Understanding this will help identify the patients who are at greater risk of muscle wasting and also the therapies that will best treat them.
Approaches To Therapy For The Skeletal Muscle Actin Diseases
Funder
National Health and Medical Research Council
Funding Amount
$912,078.00
Summary
We have shown that errors in a crucial muscle protein called actin cause muscle diseases that affect newborn children. These diseases are mainly very severe, causing death within the first year of life. Currently there is no cure. This project will investigate possible therapies for these diseases, such as viral delivery of a normal version of actin and finding a drug to overcome the weakness. Successful outcomes will crucially bring treatment closer for the patients.
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.
The Influence Of A-actinin-3 On Muscle Structure, Metabolism, Performance And Response To Diet And Disease
Funder
National Health and Medical Research Council
Funding Amount
$624,355.00
Summary
We have identified a common genetic variant that results in absence of the fast muscle fibre protein a-actinin-3 in more than one billion humans worldwide. Loss of a-actinin-3 influences elite athletic performance, muscle bulk and strength in the general population, response to diet and exercise, and susceptibility to developing type 2 diabetes. We will now study mice and humans to determine how this gene influences variations in human performance, metabolism and severity of muscle disease.