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Last Updated: Friday, 1 April, 2005, 22:58 GMT 23:58 UK
Hope for new arthritis treatment
Image of a knee examination
Arthritis can be very painful
Inhibiting a single enzyme may be enough to block the development of arthritis, research suggests.

Scientists prevented the gradual loss of protective cartilage around the joints that leads to arthritis by modifying a gene for a key enzyme.

The US and Australian teams hope their work could lead to treatments to combat osteoarthritis and possibly inflammatory arthritis.

Details of the research, on mice, are published in the journal Nature.

Now that we know the enemy effective therapeutics for the management of cartilage destruction in arthritis can be developed
Dr Amanda Fosang
Cartilage contains a crucial component called aggrecan, which functions like a shock absorber, helping the tissue bear load and resist compression.

Normal healthy cartilage has lots of aggrecan, but in arthritis aggrecan is destroyed by a family of enzymes called the aggrecanases, and the cartilage loses its shock-absorbing capacity.

The researchers, from US company Wyeth and Australia's University of Melbourne and Murdoch Children's Research Institute, have discovered one particular member of the aggrecanase family, aggrecanase-2, plays a crucial role in this destructive process.

They genetically engineered mice that lacked a part of one such enzyme, aggrecanase-2.

They found that these animals were largely protected from cartilage destruction.

Drug hope

The researchers said their work is the first to show that mutations in a single gene can halt cartilage degradation.

They believe it could be possible to fight arthritis by developing drugs designed to inhibit the human form of aggrecanase-2.

Dr Elisabeth Morris, of the US team, told the BBC News website a new potential preventative treatment would be a significant breakthrough for osteoarthritis as current drugs purely focused on relieving pain.

The condition is the most common form of arthritis, and some studies suggest it may affect as many as 30% of adults.

Dr Amanda Fosang, a member of the Australian team, said the results also had implications for all forms of arthritis, including rheumatoid arthritis and juvenile arthritis.

She said: "Until now, we have not known exactly which enzyme to block.

"It is hard to fight the enemy if you don't know who the enemy is.

"Now that we know the enemy effective therapeutics for the management of cartilage destruction in arthritis can be developed."

Dr Madeleine Devey, of the UK Arthritis Research Campaign, said: "Although the studies are in mice and the experimental models used are both a very long way from the human disease, we know that this enzyme is expressed in human cartilage.

"It will be very important to determine its role in human disease."

However, Dr Devey raised doubts about the possibility that new treatments could be developed for inflammatory arthritis on the back of the latest research.

She said: "Although cartilage is destroyed in inflammatory arthritis, I rather doubt that targeting a single enzyme would have a dramatic effect as this is a consequence of the inflammatory process rather than the cause."

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