Searching for treatments for myotonic dystrophy

Dr Saam Sedehizadeh

Dr Saam Sedehizadeh, University of Nottingham, aims to bring us closer to clinical trial readiness for myotonic dystrophy type 1 (DM1). Clinical Fellow, Dr Sedehizadeh will test around 5,000 drug-like chemicals for their potential to treat myotonic dystrophy. He will also follow a group of patients to help define outcome measures and find biomarkers that could be used in future clinical trials for DM1.

What are the researchers aiming to do?

Myotonic dystrophy is the most common form of muscular dystrophy in adults and is thought to affect around 7,500 people in the UK. It exists in two forms – DM1 and DM2 – both caused by the expansion of a repeated piece of DNA code. Healthy individuals normally have up to 30 copies of the triplet repeat, but individuals with DM1 can have many hundreds of copies. Myotonic dystrophy causes muscle weakness and stiffness but can also affect other parts of the body causing, for example, cataracts and abnormalities in the heart, brain and hormonal systems.

In the simplest terms, a cell is a little like a fried egg. The yolk is the nucleus – where the DNA is stored – and the white is the cytoplasm, where proteins are made. In order for the cell to make a protein, the instructions that are in the DNA must be taken from the nucleus to the protein-producing machinery in the cytoplasm. The cell does this by creating a messenger molecule called RNA. It is thought that in DM the expanded repeats cause the RNA to become trapped in the nucleus in small clumps that can be seen under the microscope. The trapped RNA binds to proteins in the nucleus and prevents them carrying out their normal function. In particular, a protein called ‘muscleblind’ is trapped in these clumps. This protein is involved in the processing or “splicing” of several genes which have important roles around the body, such as controlling muscle contraction.

Dr Sedehizadeh, is going to screen a library of 5,000 drug-like chemicals for their potential to treat DM1. Using a specially devised drug screen consisting of cells grown in the laboratory, he will test whether any of the 5,000 drug-like chemicals are able to reduce the number of clumps and help the trapped RNA get out of the nucleus. This part of Dr Sedehizadeh’s project will build on work previously funded by Muscular Dystrophy Campaign and carried out by Prof David Brook – Dr Sedehizadeh’s supervisor. You can find out more about this project here. Any of the chemicals that have potential as a treatment will be further tested in animal models to confirm their ability to disrupt the clumps of RNA.

In addition to the drug screen, Dr Sedehizadeh will be studying patient samples and following up a group of patients with DM1. For clinical trials to be successful, it is important for the researcher to have well defined outcome measures. These are signs and symptoms of the disease that if reduced by the treatment being tested, would demonstrate its effectiveness. They are often things that measurably worsen as the disease progresses. Dr Sedehizadeh aims to evaluate whether certain measures, such as the six minute walk test and muscle strength tests, in combination with determination of muscle mass and serial muscle samples might be useful in clinical trials for DM1. This will allow us to identify any biomarkers i.e. sensitive indicators of how advanced or severe the disease is, in DM1 patients. Biomarkers are used alongside outcome measures in a clinical trial to demonstrate the effectiveness of the treatment being tested.

How will the outcomes of the research benefit patients?

This research could highlight candidate drug candidates that have the potential to be used to treat myotonic dystrophy. In addition, Dr Sedehizadeh’s work should bring us a step closer to clinical trial readiness for DM1 as he will help to define outcome measures and biomarkers that could be used in any future clinical trials.

Grant information

Project leader: Dr Saam Sedehizadeh
Location: University of Nottingham
Conditions: Myotonic dystrophy
Duration: 3 years, starting 2013
Total project cost: £175,094
Official title: Therapeutics development and identification of potential biomarkers in myotonic dystrophy type 1

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 the Muscular Dystrophy Campaign.

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.

Further information and links

Download a summary of this research project

Read about our trip to Nottingham to visit Dr Sedehizadeh

Learn more about myotonic dystrophy

Read the latest research news for myotonic dystrophy


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