Discovering biomarkers for Duchenne muscular dystrophy

Professor Wood’s project aims to identify molecules which could be used as biomarkers for Duchenne muscular dystrophy. If successful, these biomarkers could be used to improve diagnosis, measure the progression of the condition more accurately and assess the benefit of drugs in clinical trials without the painful procedure of muscle biopsies. They will also develop improved methods of measuring these molecules which will be better suited for use in clinical laboratories than current methods.

This project is funded by the Duchenne forum – a collaboration established to accelerate progress in the search for treatments and eventually cures.

MicroRNAs are small DNA-like molecules that play a major role in the control of cell functions. They are released from cells and can be found in various body fluids including the blood, and can report valuable information on the state of the cells from which they originated. Some microRNAs in the blood could therefore reveal information about the progression of a condition and could potentially be used as biomarkers (small molecules that can be easily measured and whose levels change in line with the severity and progression of a condition).This project aims to identify microRNAs which could be used as biomarkers for Duchenne muscular dystrophy.

During the first year, the student has familiarised herself with the literature and laboratory skills that will be required for the project, such as taking samples and collecting RNA and protein. She has also started analysing microRNAs in blood taken from two different mouse models, each with a different genetic mutation, to understand the effect of these mutations on the condition. This work is on-going. The next step is to look at different ages in one of these mouse models to see how microRNAs in the heart and blood change over time; this will give a better understanding of how the condition progresses in the mouse model. The mice will also be treated with a molecular patch (known as an exon skipping approach) to assess what changes occur in the blood and heart, and how much we can restore heart function at a cellular level.

During the second year, the student has continued to study the levels of a large number of proteins in different mouse models of Duchenne muscular dystrophy. The researchers were testing to see the effect of the different genetic mutations on the proteins. The initial analysis showed that the amounts of proteins are very similar in the two Duchenne muscular dystrophy mouse models. The student is now comparing young and old animals to investigate if the protein levels change with age and if this is different between healthy mice and mice that model the condition.

The student is also investigating if the progression of the condition in the heart can be related to microRNAs in the blood, so that these may be used as potential biomarkers. To do this the hearts of mice that model Duchenne muscular dystrophy have been collected at different ages and therefore reflects different stages of the condition. The heart has been separated into different functional parts.  The levels of RNA in the hearts of 24 week old healthy mice and mouse models of the condition have been measured so far. These experiments show that there are already small differences in the RNA levels between the Duchenne muscular dystrophy model and healthy mice at this age. The student also found that around a third of the RNA is at different levels in the different areas of the heart. This will help us to understand if Duchenne muscular dystrophy progresses differently in the various regions of the heart. Next the student will do the same experiments in mice of different ages.

What are the researchers aiming to do?

Biomarkers are small molecules that can be easily measured and whose levels change in line with the severity and progression of a condition. Having biomarkers for Duchenne muscular dystrophy would be useful as they could be used to monitor the condition and measure people’s response to potential new treatments, for example in clinical trials. In this project, Professor Wood and his PhD student will examine three microRNAs that are involved in the formation of muscle tissue to see if they might be suitable biomarkers for Duchenne muscular dystrophy.

MicroRNAs are small pieces of RNA (a molecular copy of a gene) that are used by cells to control which genes are turned on or off. They can sometimes be found in the blood where their levels can be measured. Professor Wood believes that the three microRNAs to be investigated are released from muscle fibres and are involved in repairing damaged muscle. This will be investigated in various models including muscle cells grown in the laboratory and animal models of Duchenne muscular dystrophy. If the microRNA levels correlate with muscle repair, they could be suitable biomarkers for Duchenne muscular dystrophy, and possibly other neuromuscular conditions.

In addition to studying the role of the microRNAs, Professor Wood and his PhD student will develop an improved laboratory method for detecting them, which could make the tests more readily available in the clinic.

Speaking about the grant, Professor Wood said:

We are very grateful that the Muscular Dystrophy Campaign has decided to support this PhD project which looks at the levels of microRNAs for Duchenne muscular dystrophy. These microRNAs are short pieces of RNA which may be detected in blood. Certain microRNAs change following treatment so we want to use them as biomarkers as it provides an easy and non-invasive way of looking at how well a treatment is working. We are hoping to expand on this and find even better biomarkers.”

How will the outcomes of the research benefit patients?

Knowledge from this project will be vital in understanding how the three microRNAs under investigation influence muscle function. It will also reveal whether these molecules have the potential to be used as meaningful biomarkers for Duchenne muscular dystrophy (and possibly other muscular dystrophies). If successful, these biomarkers could be used to improve diagnosis, measure the progression of the condition more accurately and assess the benefit of drugs in clinical trials without the painful procedure of muscle biopsies.

The development of an improved method for measuring the microRNA levels from blood samples will pave the way for such tests being more readily available.

Grant information

Project leader: Professor Matthew Wood
Location: Department of Anatomy, Oxford University
Conditions: Duchenne muscular dystrophy
Duration: 4 years, starting 2014
Total project cost: £ 110,231
Official title: Serum MicroRNA Biomarkers of Duchenne Muscular Dystrophy: Biological Significance and Diagnostics Development

Further information and links

Download a summary of this research project

Read about other Duchenne muscular dystrophy research projects we are funding

Read the latest research news for Duchenne muscular dystrophy

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