Background
In Duchenne muscular dystrophy muscles become damaged and are replaced with fat and scar tissue, which prevents the muscle from functioning properly. This process is known as fibrosis and is an indication of the condition progressing.
To tell if a treatment is having an effect, clinicians need sensitive methods of measuring how a condition progresses, these are referred to as ‘outcome measures’. Physiotherapy-based measurements of muscle strength and function are the most commonly used outcome measures in clinical trials. However, these measurements may be affected by other factors, such as stiffening joints, motivation, and understanding of how to do the test. Measuring the amount of fibrosis in muscles could be an alternative outcome measure.
What are the aims of this project?
In this project Professor Straub and his team at Newcastle University are investigating if magnetic resonance imaging (MRI) can be used to accurately detect and measure fibrosis. MRI allows clinicians to take images of internal body structures, such as muscles, but at present it is not possible to accurately measure how much fibrosis there is within muscle.
To highlight and measure fibrosis, the researchers will inject ‘EP3533’, into a mouse model of Duchenne muscular dystrophy. EP3533 is a substance which binds to areas of fibrosis and alters the MRI image. Using MRI and EP3533 the researchers will measure the amount of fibrosis in the muscles and heart of young mdx mice. To see how accurate the MRI measurement is, they will compare it to well established laboratory-based measurements of fibrosis which depend on surgery to obtain the tissue.
Next Professor Straub and his team will investigate how sensitively MRI can assess the progression of the muscular dystrophy by measuring changes in the amount of fibrosis in response to a treatment. The researchers will use MRI and EP3533 to detect the amount of fibrosis in the muscles of mdx mice before and after treatment with Halofuginone, a treatment being developed to reduce fibrosis. They will also study mice who are not given any treatment. Comparing the fibrosis measured by MRI in the treated and untreated mice should indicate how well the method can detect changes in fibrosis following treatment with a potential therapy.
Why is this research important?
Now that treatments for Duchenne muscular dystrophy are being tested in clinical trials there is a need for accurate ways to measure if treatments are effective. If this project shows that MRI (using EP3533) can accurately measure changes in fibrosis in response to treatments, it would suggest that these could be used to detect fibrosis as an outcome measure in clinical trials.
It could also provide a useful tool for researchers to get a better understanding of fibrosis in neuromuscular conditions.
How will the outcomes of this research benefit people with Duchenne muscular dystrophy?
This research could lead to a new, non-invasive outcome measure for Duchenne muscular dystrophy. This would help in the assessment of potential new treatments for people with Duchenne muscular dystrophy. However, it is important to note that it would be necessary to test EP3533 in clinical trials to show that it is safe for use in humans first.
If accurate and safe, this tool could also provide information on how an individual’s condition is progressing. This could therefore help to inform how different symptoms, such as fibrosis in the heart muscles, are managed.
How might this research impact on other neuromuscular conditions?
Fibrosis is a symptom of many muscular dystrophies and contributes to muscle weakness in these conditions. If shown to be an accurate way to measure fibrosis, this technique could also be investigated as an outcome measure in other neuromuscular conditions with fibrosis.
Grant Information
Project leader: Professor Volker Straub
Institute: Newcastle University
Conditions: Duchenne muscular dystrophy
Duration: One year, starting 2017
Total cost (£): 29,950
Official title: Assessing muscle fibrosis by magnetic resonance imaging
Further information
Read about our other Duchenne muscular dystrophy research projects
Read our research news stories on Duchenne muscular dystrophy
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