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New research sheds light on the cause of myotonic dystrophy type 1

15 December 2022

Research findings from the University of St Andrews have linked myotonic dystrophy type 1 to an issue with the mechanism that controls stress response in cells in the body.

A better understanding the root cause behind this condition will in time lead to more targeted and effective therapies and treatments.

What is myotonic dystrophy type 1?

Myotonic dystrophy type 1 (DM1) is an inherited condition, which affects muscles and other parts of the body (for example the eyes, heart and hormonal system).

Symptoms most commonly associated with DM1 are myotonia (muscle stiffness), muscle-wasting, problems with heart, bowel and brain, as well as lens cataracts. DM1 is estimated to affect about one in every 8,000-20,000 people around the world. The typical onset varies between people, and it is often milder the later the first symptoms appear.

What causes it?

DM1 is caused by changes in the gene for DM1 protein kinase (DMPK1). These changes result in the formation of longer copies of DMPK1 RNA. The purpose of RNA is to translate information from DNA into proteins, but when these longer copies are formed, they clump and become trapped in the nucleus.

The DMPK1 clumps attach to a protein that is involved in controlling how genes work and where they are in the cell (called MBNL1). The DMPK1 clumps are bad for the cell because they prevent MBNL1 from doing its job, which ultimately leads to the onset of DM1 symptoms. However, how DMPK1 clumps cause cellular damage, and how that leads to DM1 symptoms, are currently not understood.

Uncovering the mystery – the connection between MBNL1 and DM1

Researchers at the University of St Andrews led by Dr Judith Sleeman have previously shown that MBNL1 is normally found in small cytoplasmic structures that help cells recover from stress – called paraspeckles. Paraspeckles are formed when the cell is stressed and go away again once the stress has passed.

People living with DM1 have less MBNL1 in their paraspeckles, so the researchers hypothesised that most of the MBNL1 could be trapped in the DMPK1 clumps. This study focused on understanding the differences where MBNL1 is found between people with DM1 and people who do not have the condition, and how changes in localisation affects MBNL1’s ability to do its job.

During their detailed investigations, the researchers uncovered that only a small fraction of MBNL1 was attached to DMPK1 clumps in the cells of people with DM1. However, Dr Sleeman and colleagues observed that the formation of paraspeckles is delayed in response to stress.

Interestingly, the paraspeckles go away quickly upon cell recovery from stress in cells derived from people with DM1. This is important as it points towards mistakes in the mechanism controlling stress response in cells from people with the condition.

What this means for the future

These findings are important because they give us a more thorough understanding of complex mechanisms that cause DM1. They also underline the need for more studies and research into this area.

These findings present us with an important piece of the large puzzle behind the causes of DM1. Although this type of research may appear abstract at first, it is a critical step in understanding the causes of conditions (in this case, myotonic dystrophy type 1), which will eventually lead to more targeted and effective therapies and treatments.

‘What’s new in research’ is our monthly blog series that will feature recent advancements in research into muscle-wasting conditions. Each month, a research article will be summarised for you by our research communications volunteers, all of whom have backgrounds in various fields of research.

This piece is written by Yiru Chen. ” Yiru is studying for a BSc (Hons) in Materials Science and Engineering at the University of Manchester. She got involved in writing for MDUK because she is enthusiastic about scientific studies that will improve lives. She wants to utilize her scientific knowledge to get more people to understand and pay attention to muscle-wasting conditions.

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