Osteoarthritis (OA) is caused by loss of joint cartilage.
The big question is "Can we prevent that cartilage loss?"
Why is this important?
OA is the most common form of arthritis. It affects around 8m people in the UK alone.
It is characterized by pain and reduced mobility often resulting in knee or hip replacement.
OA creates a huge health economic burden on society
What are the aims of this research?
OA is caused by loss of joint cartilage. Cartilage is lost when abnormal 'wear and tear' on a joint stimulates the production of an enzyme called MMP1. MMP1 causes the breakdown of collagen resulting in cartilage loss.
To block MMP1, inhibiting collagen break down, preserving the cartilage.
What does this research involve?
First of all we worked out the molecular structure of MMP1.
Then we screened thousands of molecules to identify one that would prevent MMP1 breaking down collagen.
These candidates had to be extremely effective (or 'potent'). Also, they must interfere specifically with MMP1 for collagen and not other matriptase inhibitors (MMPs). They must be 'highly specific' - otherwise they interfere with other normal processes leading to side effects.
The best candidate drug we have found is called NEW1066.
It has now been tested in test-tubes ('in vitro') and shown to be both potent and specific.
And it has been tested in mice and shown to be highly effective in preventing cartilage loss.
We now want to test NEW1066 in humans. Currently our research is directed at ways to deliver this drug effectively to the cartilage in humans prior to the first clinical trials in man.