Muscular dystrophy: keeping muscle cells intact

Muscular dystrophy is a devastating illness. With no cure, the UK’s estimated 20,000 sufferers face the bleak prospect of slowly losing their mobility and independence.(1) Sadly, some also expect to die early. Researchers are investigating whether a drug called Poloxamer 188 can help keep muscle cells intact. If so, their work could eventually lead to clinical trials of the drug.

What's the problem and who does it affect?

Currently there is no cure for muscular dystrophy

Many people withmuscular dystrophy must face up to the fact that their health will slowly deteriorate, making life increasingly difficult. As their muscles gradually waste away, they will get weaker and weaker.

Most people try to keep things as normal as possible. But many need to use a wheelchair, and they may need help to breathe and a full-time carer to help them eat, wash and perform everyday tasks that others do without thinking. Sadly, some will lose their lives to their illness.

There are many different types of muscular dystrophy. They vary in the age of onset, the severity of the symptoms and the rate of progression. Duchenne muscular dystrophy is the commonest and most severe. About 100 boys are born with the condition each year in the UK.(2)

Many parents find it very difficult to come to terms with a diagnosis of Duchenne muscular dystrophy. It’s shocking to discover that your son will probably need to use a wheelchair in his teens and may well die before reaching his thirties. Parents and sufferers alike are desperate to find a cure.

What is the project trying to achieve?

Repairing damage to muscle cells

Most forms of muscular dystrophy are caused by faults in genes that are responsible for the structure and function of muscles. The cell membrane, which surrounds each muscle cell, is very important in keeping muscles healthy. Recent studies have made it clear that a lack of stability in these membranes is a major cause of the muscle wasting seen in people with Duchenne muscular dystrophy, as well as in many other forms of the condition.

This team of researchers is performing laboratory tests to find out whether a drug called Poloxamer 188 can help repair damaged cell membranes in skeletal muscle. They will study both Duchenne muscular dystrophy and a rarer form of the condition, called dysferlinopathy.

Poloxamer 188 acts as a membrane sealant. Another group has already shown that it can have a protective effect on damaged muscle cells from the heart.

What are the researchers' credentials?

The Newcastle Muscle Centre, led by Professor Kate Bushby (right) and Professor Volker Straub, is a world-renowned centre for the diagnosis and management of muscular dystrophies and related disorders. It is a 5* research organisation – the highest possible rating – with an excellent track record in human genetics, and occupies a new, purpose-built facility in the centre of Newcastle.

With the emphasis in muscle disease moving increasingly from diagnosis to novel treatments, this project will build on the expertise of the project team.A close interaction between the laboratories and clinics will allow any promising experimental work to move as quickly as possible into the clinical arena.

Who stands to benefit from this research and how?

Striving to find a drug that prevents muscle wasting

Researchers emphasise that their work is in the early stages of development. This study will show whether Poloxamer 188 reduces damage to cell membranes in laboratory models of muscular dystrophy. If Poloxamer 188 shows promise, then researchers plan further investigations and, eventually, clinical trials.

The 20,000 people who have muscular dystrophy in the UK are still waiting for a cure. Sadly, the longer they wait, the more advanced their disease becomes. But it’s possible that some of them may benefit from this project in the future. In theory, if Poloxamer 188 can repair damaged cell membranes in skeletal muscle, it may be able to prevent the muscle wasting seen in many different forms of muscular dystrophy.

References

1. Unpublished data held by Professor K Bushby
2. Emery AEH, Muntoni F. Duchenne Muscular Dystrophy. 3rd Edition. Oxford University Press. 4 September 2003. ISBN 0198515316