Understanding variation in the effects of myotonic dystrophy type 1 on the brain

Clinical Research Fellow, Dr Hamilton and his team will investigate how the genetic changes that occur in myotonic dystrophy type 1 affect the severity of the brain-related symptoms associated with the condition such as impairment of thinking and excessive sleepiness. A better understanding of how genetic factors relate to the effects of myotonic dystrophy type 1 on the brain will help to identify new strategies for the treatment of these extremely debilitating symptoms. In addition, improved understanding of the variation in symptoms between individuals will be valuable in designing future clinical trials.

Over 80% of the required participants with myotonic dystrophy, and almost 50% of participants who are not affected by the condition (to compare the tests to) have been recruited so far.  The participants have completed tests on memory and thinking and have answered questions about their symptoms and how these impact their daily life.  Over 30 participants have had MRI brain scans to allow the researchers to look at the structure of the brain. The first sleep studies have been started.

Blood samples from the participants have been collected and will be used for DNA analysis. This will allow the researchers to compare the symptoms to the genetic changes. Samples have also been added to the MRC Neuromuscular Biobank in Newcastle, providing a valuable resource for other research groups working on myotonic dystrophy both now and in the future.
The researchers have also been studying a protein called cardiac troponin I in the blood of over 100 people with myotonic dystrophy.  Their results suggest that measuring levels of this protein may help cardiology doctors to screen for heart problems related to the condition.

The results of this work have been presented at the International Congress for Neuromuscular Disorders conference in Toronto and have been published in the scientific journal, PLOS ONE. Read our lay summary of Dr Hamilton’s results.

What are the researchers aiming to do?

Myotonic dystrophy type 1 is an extremely variable inherited condition causing muscle weakness. It may also affect other organs such as the heart, eyes and the brain. The effects on the brain can result in slowed thinking and extreme sleepiness. These symptoms can have profound impacts on the quality of life of people affected and their families.

The condition is caused by an increase in the number of DNA repeats in the DMPK gene. A larger number of repeats is associated with more severe symptoms and an earlier age of onset. The number of repeats frequently increases from one generation to the next causing more severe symptoms and earlier age of onset in succeeding generations. The number of repeats is also seen to increase throughout the life of the person affected. Blood tests that are currently used to diagnose the condition only measure the approximate number of repeats and take no account of the changes during the person’s life.

In this study, Dr Hamilton and his team will use a more accurate method of measuring the genetic changes that occur throughout the life of a person affected by myotonic dystrophy type 1. The researchers will determine how the genetic changes relate to the severity of the brain-related symptoms using brain scans, sleep studies and tests of memory and thinking. They will then look at how changes in specific structures of the brain relate to impairment of different aspects of thinking and sleep.

How will the outcomes of the research benefit patients?

The results of this study may allow the patients and their families to be offered more specific information about how the condition is likely to affect them in the future based on their genetic results. Understanding how genetic changes and changes in brain structure relate to the symptoms of the condition will also help identify mechanisms that can be targeted by drugs in the future. In addition, this work will further improve readiness for clinical trials in myotonic dystrophy by providing new insights into why symptoms vary so considerably between individuals and by revealing better clinical tests to determine if new therapies are effective in treating the brain symptoms.

Grant information

Project leader: Dr Mark James Hamilton
Location: University of Glasgow
Conditions: myotonic dystrophy type 1
Duration: three years, starting 2015
Total project cost: £215,333
Official title: Structural CNS changes, neuropsychological impairment and sleep disorders in type 1 myotonic dystrophy – a genotype-phenotype study

Dr Hamilton’s work is being funded by the Lord Attenborough Fellowship Fund, which was created to recognise the huge contribution Lord Attenborough made to the charity for over 50 years. The fund supports researchers in their specialisation into neuromuscular conditions and hope to raise £180,000 over three years. We are very grateful for the continued support from Lord Attenborough’s friends and family for enabling and promoting this Fund. Find out more about the Richard Attenborough Fellowship Fund and how to donate to it.

The project is also co-funded with the Chief Scientific Office in Scotland.

What is a Clinical Fellowship?

Clinical Training and Research Fellowships (CTRF) are available to encourage clinicians into an academic research career in the field of muscular dystrophy and related muscle diseases. They are open to medical graduates, usually during specialty training, and aim to provide an opportunity for training in clinical and/or laboratory research techniques in a project that demonstrates clear relevance to the aims of Muscular Dystrophy UK.

Clinical Fellowships are ideally placed to promote our strategic aim of funding translational research. This is the “bench-to-bedside” transfer of promising technology into a patient benefit and can be a particularly challenging process. The clinical fellows have one foot in the laboratory and one foot in the clinic giving them the unique opportunity of aiding this process and helping with the development of treatments.

We hope that the clinical fellows will take the skills and knowledge they acquire during this training to benefit patients and families at clinics where that expertise might otherwise have been lacking.

For further information

Download a summary of this research project

Learn more about myotonic dystrophy

Read about other myotonic dystrophy research we are funding

Read the latest research news for myotonic dystrophy

It is only through your contributions that we can continue to fund the vital work that takes us closer to finding treatments and cures for muscle disease. Donate now and help change the lives of thousands of people living with muscle disease. Thank you for your support.

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