A Portsmouth scientist is hoping his research will eventually buy some precious time for the boys who suffer from a rare disease which first disables them and ultimately ends their lives.
Professor Darek Gorecki, of the University of Portsmouth’s science faculty, has been awarded more than £150,000 by the Muscular Dystrophy Association USA. It is the world leading non-profit health agency dedicated to finding treatments for muscle diseases and providing patient and family support.
He and his team aim to find a treatment that would delay the onset and slow down the progression of muscle degeneration in people with Duchene muscular dystrophy, the most common and severe of all muscular dystrophies.
Duchene muscular dystrophy affects one in every 3,500 boys. It is an inherited disease and diagnosed in pre-school children. It affects mainly boys because boys have just one copy of the X chromosome, on which the affected gene is located. In girls, who have two X chromosomes, the healthy X overrides the defective gene. By the age of 12 most patients will be unable to walk, and within a few years they will lose the use of their muscles, with the exception of some small ones, for example those which control the eyes and fingers.
The condition is caused by a lack of dystrophin, a protein which acts like scaffolding and an anchor in muscle cells and without which these cells become damaged and then progressively lost. There are also brain forms of dystrophin that, when mutated, are responsible for the cognitive problems sometimes also seen in this condition.
Advances in supportive care have ensured that patients with Duchene muscular dystrophy are living longer than ever before, often well into adulthood. However, there is no cure and disease-modifying treatments are urgently needed.
Professor Gorecki said: “I am really pleased we have won this grant. It allows us to continue research based on our original discovery that altered functions of a specific molecule present on dystrophic muscle cells, called P2X7, contribute to the dystrophic muscle damage.
“We’re hoping to find a way of delaying the process of muscle degeneration in these boys. Just making them able to walk until the age of say, 18 rather than 12 – it’s quite a little thing to ask, but difficult to achieve.”
The research team has already studied the results of manipulating this molecule in dystrophic mice and found significant improvements in the disease symptoms.
Professor Gorecki said: “We know that abnormal function of this P2X7 molecule is responsible for at least some of the muscle damage seen in people with dystrophy. This grant from the MDA allows us to study the mechanism by which this happens. Understanding this mechanism may give us a new handle on treatment of this disease.
“We are also aiming to block this molecule using drugs already in trials for use in humans to treat different diseases.
“If we can achieve improvement in the mouse model of Duchene muscular dystrophy, then there is a good chance that the same treatment may work in patients, though of course, it will still need to be tested in clinical trials in humans.
“How much medicine would be needed, how young the patient would have to be for it to have any effect, how much effect it would have – all these things are unknown.”
The team’s success at manipulating P2X7 and their plans for further research received strong endorsement from a panel of the world’s leading experts in muscular dystrophy at TACT (Treat-NMD Advisory Committee on Therapeutics).
The grant will be used to fund a post-doctoral researcher, Dr Christopher Young, for three years. It will also allow the team to continue collaborations with teams in France and Belgium who have expertise in proteomics and advanced microscopy.
Professor Gorecki has spent 20 years studying the molecular pathology of Duchenne muscular dystrophy and the cognitive impairment associated with the disease. He discovered one of the brain dystrophins and identified specific areas where these are present. He is recognised worldwide as a leading expert in the condition.