Repairing injured knees and protecting against arthritis could be one step closer after scientists discovered how to block a key protein linked to ageing.
Arthritis is a common condition that causes pain and inflammation in a joint and affects millions of people in the UK. There is currently no cure.
But experts at Stanford University have developed a new drug that could reverse age-related cartilage loss and prevent knee arthritis from developing after injury.
Injury can happen when cartilage tears, often due to heavy impact during sporting activities or simply twisting the knee. Once cartilage has been damaged, it cannot heal on its own.
This can lead to pain, swelling and stiffness, and bone rubbing on bone, altering the shape of the joint and forcing the bones out of their normal position.
But researchers found injecting the drug directly into the affected joint triggered cartilage regeneration, pointing toward future therapies that could replace joint surgery.
Professor Helen Blau, an expert in microbiology and immunology and study lead, said: ‘This is a new way of regenerating adult tissue, and it has significant clinical promise for treating arthritis due to aging or injury.
‘Millions of people suffer from joint pain and swelling as they age. It is a huge unmet medical need.
Osteoarthritis affects nearly 10 million Britons. The condition causes the protective cartilage on the end of bones to break down over time, leading to pain, swelling and problems moving the joint as bone rubs against bone
‘Until now, there has been no drug that directly treats the cause of cartilage loss.
‘But this gerozyme inhibitor causes a dramatic regeneration of cartilage beyond that reported in response to any other drug or intervention.’
In the study, researchers pinpointed a protein called 15-PGDH, a type of enzyme called a gerozyme that is found naturally in the body.
Its presence increases with age and has been linked to a gradual decline in tissue function.
In mice studies, higher levels of the protein have been associated with declining muscle strength with age. Researchers found blocking the enzyme successfully boosted muscle mass and endurance in older animals.
In contrast, forcing younger mice to produce more of the protein results in muscle shrinkage.
Under normal conditions, articular cartilage – which allows the hip, knee, shoulder and ankle joints to move smoothly – has very limited ability to regenerate once it has been damaged as a result of injury or simply old age.
But the researchers found that by blocking the protein – which in turn increased levels of a hormone essential for muscle stem cell function – resulted in cartilage regeneration in older mice.
The team injected the mice in the abdomen and then directly into the knee joint with a protein inhibitor. In both cases, cartilage that had worn away with age was seen to thicken.
Over half of cases are in the knees and over 100,000 people a year end up on the NHS waiting list for joint replacement surgery
They observed similar benefits in mice with knee injuries resembling ACL tears, which can increase the risk of agonising osteoarthritis, a degenerative joint condition where the cartilage becomes so thin that knee bones grind together.
Remarkably the team found that mice who were injected twice-a-week with the drug for four weeks after injury occurred were significantly less likely to develop osteoarthritis and were able to place more weight on the injured leg.
Mice who were given a control treatment developed the debilitating condition within just four weeks.
Researchers also noted a broad return to a more youthful cartilage profile in treated mice, who expressed less inflammatory markers.
The team also tested cartilage taken from patients undergoing knee-replacement surgery for osteoarthritis.
After just one week of treatment, human tissue showed early signs of cartilage regeneration and fewer signs of inflammation and degradation.
Dr Nidhi Bhutani, professor of orthopedic surgery and study co-author concluded: ‘The mechanism is quite striking and really shifted our perspective about how tissue regeneration can occur.
‘It’s clear that a large pool of already existing cells in cartilage are changing their gene expression patterns.
‘And by targeting these cells for regeneration we may have an opportunity to have a bigger overall impact clinically.’
Prof Blau added: ‘Phase one clinical trials of a 15-PGDH inhibitor for muscle weakness have shown that it is safe and active in healthy volunteers.
‘Our hope is that a similar trial will be launched soon to test its effect in cartilage regeneration.
‘We are very excited about this potential breakthrough. Imagine re-growing existing cartilage and avoiding joint replacement.’
