The role of agrin in the cause and treatment of osteoarthritis
Lead applicant - Professor Francesco Dell'Accio
Organisation - Queen Mary University of London
Type of grant - Research Award
Status of grant - Active
Amount of the original award - £596,018.83
Start date - 1 December 2017
Reference - 21515
What are the aims of this research?
A molecule in cartilage and nerves, called agrin, is important in supporting the health of cartilage cells and helps with cartilage formation. However, in osteoarthritis, agrin is lost in both the nerves and the cartilage, potentially resulting in the pain and damage seen. The researchers aim to see how agrin is lost in osteoarthritis and how this contributes to nerve invasion and breakdown of the cartilage.
Why is this research important?
People with osteoarthritis may experience two different types of pain. One is a recurrent pain often felt whilst pressure is applied to the joint, which signals tissue damage and acts to prevent further injury. The second type is a more constant pain that occurs due to nerves being oversensitive or changes in pain processing, rather than actual damage to the joint. This is called neuropathic pain, and can remain even after joint replacement.
It is known that agrin breakdown can cause this neuropathic pain in a number of ways if lost from the nerves or cartilage. For example, healthy cartilage doesn’t normally contain nerves so can’t hurt, but when agrin is lost in osteoarthritis it allows for invasion of nerves that cause pain. However, how the agrin is lost and activates pain nerves is unknown, so the researchers will use samples from people, and mice with osteoarthritis, to answer this. They will also see whether replacement of agrin reduces pain in osteoarthritis, which could be important in identifying a new method of pain relief.
How will the findings benefit patients?
Ideally, it would be advantageous to discover drugs that as well as relieving pain and preventing increased damage to the joints, could also start to encourage cartilage regeneration. This research will identify if agrin could be used to help relieve pain symptoms in osteoarthritis as well as help protect cartilage from further damage.