Reducing muscle scarring in Duchenne muscular dystrophy

Dr Linda Popplewell and her team at Royal Holloway University will develop an antibody that targets muscle scarring (fibrosis) and test it in cell and mouse models with Duchenne muscular dystrophy. Fibrosis is a common feature of muscular dystrophies, so this research could lead to a potential treatment for many people with muscular dystrophies.

“I am really excited by this funding and look forward to a fruitful collaboration with a pharmaceutical company aimed at accelerating an anti-fibrotic therapy to clinical trial.”

The pharmaceutical company the researchers have partnered with has created several antibodies that bind to the fibrotic protein. These now need to be tested in cells in a dish to see how well they reduce scarring (fibrosis).

The PhD student has learned how to do a particular experiment that will be used to test the antibodies. This involves scratching a layer of cells and seeing how well the cells grow back – a process that mimics fibrosis. Now that this experiment is running reliably, the next step is to test the company’s antibodies and see which one is best to put forward for further testing in a mouse model.

What are the aims of the project?

Duchenne muscular dystrophy is caused by a lack of dystrophin protein. Without dystrophin, the muscle fibres break down over time and get replaced with fat and scar tissue (fibrosis). The presence of fibrotic tissue in muscle prevents proper function and repair.

The aim of this PhD studentship is to develop an antibody therapy that reduces muscle fibrosis. An antibody is a protein that recognises and binds to a specific protein.

In collaboration with a pharmaceutical company, Dr Linda Popplewell and her team will create an antibody that binds to and blocks the activity of a particular fibrotic protein that has been previously shown to be associated with kidney fibrosis. Blocking activity of this protein has not yet been tested in muscle.

The researchers will test the antibody in a particular cell model that mimics fibrotic muscle tissue. They will also test it in the mdx mouse model, alone and in combination with a gene therapy that increases dystrophin levels (micro-dystrophin gene therapy).

Why is this research important?

Although therapeutic approaches that increase dystrophin levels – such as exon skipping – are in clinical trials, it is not yet known how effective they are at combating fibrosis in people with Duchenne muscular dystrophy. This research aims to develop an anti-fibrotic therapy that can be used in combination with therapies that target dystrophin, which could potentially lead to better therapeutic outcomes.

How will the outcomes of this research benefit people with Duchenne muscular dystrophy?

This project could lead to the development of a treatment that prevents or slows down muscle fibrosis in people with Duchenne muscular dystrophy. This could potentially be used in combination with other therapies to give an even greater benefit.

Fibrosis occurs not only in skeletal muscle but also in the heart of people with Duchenne. An anti-fibrotic therapy could therefore be helpful in preserving cardiac function, in addition to skeletal muscle function.

How might this research impact on other neuromuscular conditions?

Muscle fibrosis is a common feature of muscular dystrophies, so the findings of this project could be relevant to many people living with a type of muscular dystrophy.

Grant information

Project leader: Dr Linda Popplewell
Institute: Royal Holloway University of London
Condition: Duchenne muscular dystrophy
Duration: Four years
Total cost (£): 113,857
Official title: Targeting skeletal muscle fibrosis through immunological blockade

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