Scientists identify new disease treatment path

The researchers say this previously unrecognised mechanism could have far reaching effects for the understanding and treatment of diseases including cancers and inflammatory diseases, as well as Duchenne muscular dystrophy.

The discovery was made by Dr Chris Young and a team of researchers led by Professor Darek Gorecki, as part of their on-going research into Duchenne muscular dystrophy.

It was already known that tissue damage causes the release of certain chemicals to act as a danger signal to the body. This signal is received by the so called ‘danger receptor’, a protein with the scientific name of P2X7.  However, the functions of this receptor have remained one of the great mysteries of cell science.

Professor Gorecki’s group studied dystrophic muscle cells - cells that are deteriorating due to a disease known as Duchenne muscular dystrophy. The group is the first to find that the P2X7 receptors found in dystrophic cells can react to the danger signal sent by tissue already damaged by the disease.

The same team has now discovered that in dystrophic muscles P2X7 instigates a switch in what would otherwise be a normal healthy metabolic process known as autophagy (from the Greek for ‘self- eating’).

Autophagy is the “quality-control” process, which recycles unneeded or damaged proteins for re-use within the cell. Unfortunately, when P2X7 is activated in dystrophic cells, the autophagy machinery starts eating healthy and essential proteins, resulting in uncontrolled death of otherwise intact muscle cells present near damaged cells.

By using drugs already cleared for use in treating other diseases, including arthritis, Professor Gorecki hopes to block the ‘danger receptor’ and therefore preventing autophagy turning bad.

Professor Gorecki said: “We know that abnormal function of this P2X7 molecule is responsible for at least some of the muscle damage seen in dystrophic cells, but so far the effects of P2X7 receptor shut down in combating muscular dystrophy has only been proven in mouse models.

“What we want to find out now is whether blocking this receptor with medicines would cause overall improvement and promote the good side of autophagy.”

Duchenne muscular dystrophy affects one in every 3,500 boys. It is an inherited disease and diagnosed in pre-school children. It affects boys because they have just one copy of the X chromosome, on which the affected gene is located. By the age of 12 most patients are unable to walk, and within a few years they lose the use of their muscles, with the exception of some small ones, for example those which control the eyes and fingers.

Advances in supportive care have ensured that patients with Duchenne muscular dystrophy can live into adulthood but there is no cure for the condition.