Melbourne team in arthritis find

A Melbourne research team has dead-heated with US giant Wyeth Pharmaceuticals in the race to identify the elusive enzyme that destroys cartilage in inflammatory arthritis, but has been beaten to the IP punch by the big Boston-based pharma.

Researchers from the Murdoch Children's Research Institute (MCRI) and the University of Melbourne have identified a protease, ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motif 5) as the elusive cannibal that digests cartilage in arthritis.

The study leader, MCRI and University of Melbourne of researcher Dr Amanda Fosang, said her team's research in a mouse model of inflammatory arthritis has shown that it is ADAMTS5 that attacks the major component of cartilage, the water-swollen glycoprotein aggrecan.

Aggrecan consists of about 10 per cent protein, and 90 per cent of the carbohydrate chondroitin sulfate, a popular natural remedy for arthritis. "Researchers have known for decades that the loss of aggrecan from cartilage is the first sign of the onset of arthritis," Fosang said.

She said ADAMTS5 belongs to a new family of proteases, discovered only in 1999, that digest extracellular substrates like collagen, aggrecan and the blood-clotting protein Von Willebrand's factor.

Fosang said one of the exciting aspects of the discovery is that the enzyme attack on aggrecan appears to be a common feature of different forms of arthritis, including inflammatory and rheumatoid arthritis.

Wyeth researchers co-discovered ADAMTS5, using a different mouse model -- not of inflammatory arthritis, but of osteoarthritis, the common, age-related form of arthritis.

The Melbourne University-MCRI paper was published back to back with the Wyeth paper in this week's issue of Nature.

Fosang said that now the enzyme had been identified as a potential therapeutic target, Wyeth should be able to develop drugs to inhibit or prevent arthritis.

The latent enzyme is expressed in arthritis patients and in healthy individuals, but the extent to which it is active in joint disease is unknown. Fosang said it is likely there are endogenous inhibitors as well as activators of the enzyme. The MCRI research team is now working to determine how the enzyme is regulated.

Inflammatory arthritis is a common, debilitating disorder in children. Clinicians at the Royal Children's Hospital have been treating a four-year-old patient, Laura, who was diagnosed when she was only 11 months old, after her mother noticed she had swollen fingers, feet and ankles.

Her condition was controlled by just two injections of the immunosuppressive drug methotrexate over more than three years. She is now free of arthritis, but Fosang said the institute hoped its finding could lead to a more targeted therapy to prevent cartilage damage.