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.
Regulation Of Extraocular Myosins In Craniofacial Muscles
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Muscles which move the eyeball are highly complex and contain a special motor protein which enables them to contract with the highest speed of all muscles in the body. This protein is found also in muscles of the throat which open and close the airway during coughing, sneezing and swallowing. These muscles also make many other types of motor proteins, giving them a wide spectrum of properties. The functional advantage of having very fast muscles to move the eyes, and protect the airway by preven ....Muscles which move the eyeball are highly complex and contain a special motor protein which enables them to contract with the highest speed of all muscles in the body. This protein is found also in muscles of the throat which open and close the airway during coughing, sneezing and swallowing. These muscles also make many other types of motor proteins, giving them a wide spectrum of properties. The functional advantage of having very fast muscles to move the eyes, and protect the airway by preventing foreign bodies from entering the lungs, is obvious, but how the synthesis of this motor protein is restricted to these muscles is intriguing. Studies in limb muscles have established the principle that the type of motor protein in a muscle is determined by both the type of muscle cells and the type of innervation. Nerves can change the motor proteins in response to the pattern of use imposed by the brain via electrical impulses along its nerve supply. It is known that frequency of nerve impulses to eye muscles are exceptionally high. This project will use several approaches to test the hypothesis that the nerve impulse pattern delivered to these special muscles is involved in the regulation of this motor protein. In one approach, these muscles in rat will be subject to long-term paralysis by cutting their nerve or by the use of botulinum toxin to see if the motor protein is abolished or reduced. In another, the nerve to throat muscles which make this protein will be redirected to another throat muscle which does not normally make this motor protein. These experiments are expected to support the notion that eye and throat muscles are different from all other muscles in the body, and that the normal neural activity from nerves innervating these special muscles is necessary for inducing the synthesis of their motor proteins. These results will greatly help us understand how eye and throat muscles acquire their unique characteristics.Read moreRead less
Physiological And Pathological Effects Of Oxidation On Contractile Function In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Reactive oxygen molecules generated within muscle fibres in normal exercise and in pathological conditions, greatly affect muscle function by altering the responsiveness of the contractile proteins. This study investigates how various oxidative stresses affect particular reactive sites on key proteins controlling muscle contraction. The findings should identify key molecular changes involved in normal activity and the role oxidation plays in chronic muscle weakness in particular conditions.