Gene discovery holds key to new treatments for arthritis

The findings, which are published today in the leading scientific journal Nature Genetics, were made after researchers studied three unrelated families with a form of inherited hand osteoarthritis and discovered the mutated gene, called TRPV4.

In people with this arthritis the earliest changes appear in the hands at around five years of age and by adulthood all the joints in the fingers and toes are affected with a deforming, painful osteoarthritis.

The TRPV4 gene regulates calcium entry into the cell, and this is important for normal function of cartilage cells. Working with collaborators from the Pharmacology Department at the University of Melbourne, researchers found that when the gene is mutated, cells don't function properly, causing the arthritic condition.

Importantly, Murdoch Childrens researchers also found in a mouse model of arthritis TRVP4 gene expression was dramatically reduced, and the greatest decrease was seen in mice with the most severe arthritis, confirming that altered TRVP4 activity is associated with arthritic disease.

The discovery raises the possibility that the gene may also play a role in age or injury related arthritis.

Dr Shireen Lamande from Murdoch Childrens says the discovery could revolutionise arthritis treatment.

"We discovered that when this gene is mutated it leads to this severe form of osteoarthritis, which represents a major step forward for arthritis research. The next step for us is to understand the cell signalling pathways that are changed by the mutations and lead to arthritis. This will help us develop therapies that specifically target those pathways and prevent the disease," she said.

The gene is also expressed in nerves and is responsible for increased sensitivity to pain, meaning the finding could also have implications for people with cancer and other painful chronic conditions.

"Understanding more about how this gene works will help us understand how drug treatments will affect the different conditions caused by TRPV4 and which drugs might be best suited for each condition."

Professor Ravi Savarirayan from the Victorian Clinical Genetics Services, a subsidiary of Murdoch Childrens, the clinician involved with the study, reports that "these findings will give patients who have previously had no diagnosis for their symptoms a definitive answer and will help clarify the risk of other family members inheriting the condition.

"Even without a current treatment, a correct diagnosis is very important for family members, providing a guide to what they can expect in the future, allowing screening for their children, and paving the way to develop new treatments for their painful arthritis."

Ian Begg participated in the study, along with his family members; the Begg family have four generations who are affected with the condition.

"It's nice to know why we are the way we are, and now that the problem has been identified there may be answers that can help," Ian said.

"The condition restricts your hand movements as you get older and can cause a lot of pain, so if this discovery leads to some form of treatment it would be fantastic for future generations, the younger family members as well as me as I get older."