New research study in Scotland will investigate brain-related symptoms in myotonic dystrophy type 1


Dr Mark Hamilton is a Speciality Registrar in Clinical Genetics who is leading a new clinical research study funded by Muscular Dustrophy UK in the West of Scotland based on myotonic dystrophy type 1. He tells us more about the study. 

What is the name of the study and how has it been funded?

It’s called “The DM1-Neuro Study”. The project is being supported by a joint funding agreement between Muscular Dystrophy UK and the Scottish Government.

What is the study aiming to do?

The research study is designed to build on existing work being carried out at the University of Glasgow, led by Prof Darren Monckton. Myotonic dystrophy type 1 is caused by the expansion in size of a specific repeated sequence of genetic material (DNA). In general, we know that larger expansions of the DNA repeat are associated with more severe symptoms, although the relationship between the expansion size and disease severity has not yet been well enough described to enable individuals’ symptoms to be reliably predicted from their genetic result. Part of the reason for this is that the traditional method of measuring the DNA repeat does not accurately take account of changes that occur in the repeat throughout an affected person’s lifetime.

Prof Monckton’s team has developed a more accurate method of measuring the DNA repeat, one that does take account of these changes. Measurements using this new method have been shown to tie in much more closely with the age at which individuals experience their first symptoms compared with traditional methods. However, until now the relationship with more in-depth measurements of the effects of myotonic dystrophy have not been investigated.

The DM1-Neuro Study therefore aims to explore how these more accurate genetic measures relate to the severity of symptoms that people with myotonic dystrophy type 1 experience.

The study will look at a range of different aspects of the condition, but will particularly focus on its effects on the brain, which can result in symptoms including excessive daytime sleepiness, low motivation and difficulties with certain aspects of thinking. People in our myotonic dystrophy clinics often tell us that these symptoms are the ones with the biggest impact on relationships, employment and overall quality of life. We will measure these brain-related effects using a range of techniques including MRI scanning, questionnaires and sleep studies.

Who can take part?

We aim to have 40 individuals with the adult-onset form of myotonic dystrophy type 1 taking part, recruited from those attending annual review clinics in the West of Scotland.

As with any clinical study, there are certain criteria for participation. For example, those with cardiac pacemakers or other metalwork in their body may not be able to take part in the MRI portion of the study. If you attend a myotonic dystrophy clinic in the West of Scotland, you can ask your clinician to check your eligibility against the study criteria.

What will study participants have to do?

Everyone taking part in the study will be asked to provide a blood sample for genetic analysis. They may also be given the option to provide extra samples for the Medical Research Council Neuromuscular Biobank in Newcastle, making them available to other research groups interested in myotonic dystrophy. A member of the research team will then arrange three further sessions for measurements to be taken.

Firstly, participants will be invited to attend the Queen Elizabeth University Hospital in Glasgow for a single MRI scan of the brain. The scan takes around an hour, and in most cases it will be possible to provide a free taxi for transport.

Next, a member of the team will arrange a home visit, where the participant will be asked to perform a series of simple tasks and verbal tests, designed to assess specific aspects of memory and thinking. These take around an hour to complete. After a rest, the participant will then be asked to complete some questionnaires designed to assess how symptoms of myotonic dystrophy impact on their day-to-day life. A close friend or family member will also be asked to complete two short questionnaires to give information from their perspective.

Lastly, the research team will arrange a suitable time to undertake some sleep assessments. The researcher will visit in the evening, and ask the participant to wear some lightweight equipment including elasticated chest straps and fine plastic tubing under the nose over a single night’s sleep in their own bed. The equipment will measure the quality of sleep and detect any abnormal breathing patterns.

The researcher will then return the next morning to undertake a further test to assess the participant’s ability to resist sleep, called the Modified Maintenance of Wakefulness Test. The participant will be asked to wear the sleep study equipment again, and to lie on top of their bed in a darkened bedroom, trying not to fall asleep for 40 minutes. This test will be done at 9:30am, then repeated at 11:30am and 1:30pm.

How will this research benefit families affected by myotonic dystrophy?

There have been a number of significant advances in myotonic dystrophy research in recent years, including work towards developing drugs that it is hoped could alter the course of the condition. One such drug is currently the subject of a clinical trial in the USA. These are clearly exciting developments, but a number of challenges remain which must be overcome in order to ensure the myotonic dystrophy research community is ready to deliver effective clinical drug trials.

One major barrier to clinical trials is the wide variability of myotonic dystrophy. It varies not only in terms of the symptoms which individuals have, but also how these progress and change over time. This makes it difficult to say for certain whether differences observed between two groups in a trial are truly due to the effect of a drug, or just part of the usual variation between individuals with myotonic dystrophy type 1. By investigating the relationship between genetic measures and symptoms, our study will help determine whether genetic measures may be a useful basis for dividing patients into groups for clinical trials, enabling those whose symptoms would be predicted to progress in a similar way to be considered together.

Another important question for trials is what should be measured to determine whether a treatment is effective. This is particularly challenging when considering some of the symptoms relating to the brain. For example, we may see that a drug improves changes seen on an MRI scan of the brain, but how do we know if this in turn actually makes a difference to how that person feels and is able to function in their daily life? Our study will carry out a wide range of measures relating to these complex symptoms on a large group of people with myotonic dystrophy. Comparing results from each of these measures will help to identify those most meaningful for use as outcome measures in clinical trials.

We also hope that our study will provide new insights into the mechanisms behind key symptoms in myotonic dystrophy, helping identify new ways to treat them. Excessive daytime sleepiness is a problem for as many as 88 percent of those affected, but the cause of this often debilitating symptom is still poorly understood and, as a result, treatment options are limited. Our study will be the first to combine state-of-the-art MRI brain images with detailed measures of sleep and excessive sleepiness, improving understanding of how these symptoms arise and so bringing us closer to identifying potential targets for new therapies.

Finally, the DM1-Neuro Study will enhance existing expertise in myotonic dystrophy research in the West of Scotland, as well as strengthening links with other specialist UK research centres including Newcastle, Nottingham and London. We will also working with a team at the University of Iowa in the USA relating to the MRI portion of the study. These links will keep the UK myotonic dystrophy research community in a strong position to continue to attract further research grants and international collaborations, giving UK patients the opportunity to take part in the latest research studies and clinical trials in the future.

When should we hear the outcome of the study?

The study is funded until August 2018, although we hope to gather most of the raw results within the next year to 18 months. We will share our findings along the way by a number of means, including presentations at conferences, writing articles for scientific journals and through the Muscular Dystrophy Support Group Newsletter.


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