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Exercise is an important aspect of leading a long and healthy life – its benefits affect all parts of the human body from our major organs to our skeletal muscle.
But what if we could harness the benefits of exercise, and target and deliver them to those who need them most using a drug?
This is exactly what researchers at the Metabolic Reprogramming Laboratory have been exploring. And what they have discovered could initiate a major overhaul of how muscle-wasting diseases are treated.
The Metabolic Reprogramming Laboratory, which started in 2009, has been focused on identifying and understanding the molecular mechanisms that contribute to the adaptive response to exercise in skeletal muscle.
It is these mechanisms that contribute to the health benefits that exercise has on numerous organs and systems.
‘Our interest is in trying to understand how alterations in metabolism contribute to chronic disease and equally, how can we manipulate metabolic pathways to treat disease,’ says Professor Sean McGee who heads the laboratory.
‘What we typically see during exercise is that we turn on genes that help with how we make energy.
‘We burn glucose and burn fat, and turn on those genes every time we exercise, which is part of the reason why we get positive benefits from exercise.
‘Our reasoning was, if we discovered the molecular mechanisms mediating these genetic changes during exercise, then potentially we could tap into those mechanisms with a therapeutic.’
– Prof. Sean McGee
The team is preparing to test whether this approach is a viable therapeutic strategy for muscle wasting conditions, such as muscular dystrophy and motor neurone disease, as well as muscle wasting due to aging. These diseases are also characterised by metabolic alterations in muscle.
And much progress has already been made, the team discovered a signaling pathway within skeletal muscle that mediates gene expression changes during exercise.
“Furthermore, work by the team has shown that this pathway can be targeted using a drug, which results in exercise-like effects in skeletal muscle and positive effects on whole body metabolism,’ he says.
A paper published in 2016 showed proof of concept for this research work, which so far has only been tested on animals.
However, Prof. McGee says the data that continues to come through looks very promising and puts the research on track for human studies.
And if backed with the funding the project needs, he says clinical trials could be up and running within three to four years.
Prof. McGee says there is an urgent need for new therapies for these muscle wasting conditions, which have a devastating impact on patients.
‘We envisage this sort of therapy would initially target people who suffer from genetic muscle wasting disorders,’ he says.
‘Even though that’s a relatively small number of people, the disease impact is significant. But with more clinical data and everyday use data from this sort of therapy, it could open up the possibility of treating age-related muscle wasting, which unfortunately all of us encounter at some point in our lives. That imparts a huge burden on healthcare and carers.
‘The impact in dollar terms is in the hundreds of billions of dollars worldwide, when you think about the age care sector – it’s a bit difficult to quantify, but it would be huge.’
