A breakthrough treatment may revive busted knees and eliminate joint replacement: study

This may be just what some people kneed.

Joint issues have never been limited to the elderly, as more young people deal with debilitating knee pain and turn to surgical options for relief.

Now, a revolutionary treatment may provide relief for the joint inflammation, pain, stiffness and reduced mobility that often come with arthritis or other knee injuries.

Nearly everyone will be affected by wear and tear on the protective layer of cartilage at the ends of our bones, either by developing osteoarthritis as they age or from injuries like ACL tears, where pivoting, jumping and abruptly stopping are frequent.

The most common treatment for severe arthritis is to surgically replace the damaged joint, a costly prevention for a condition millions suffer with.

Researchers at Stanford Medicine, though, have discovered a breakthrough treatment in older mice that regrows damaged knee cartilage by restoring naturally lost cartilage and prevents osteoarthritis after knee injuries.

New, functional joint cartilage was also produced from the treatment — which was discovered by further investigating a protein that we naturally produce as we age.

The protein 15-PGDH is described as a gerozyme, or an enzyme that becomes more abundant with age and contributes to the gradual loss of tissue function.

Blocking the protein in older mice has been linked to increased muscle mass and endurance, as well as regeneration of bone, nerve and blood cells.

These tissues heal by tissue-specific stem cells multiplying and changing into specialized cells.

Not cartilage cells, though. Instead of relying on stem cells, they heal by changing their patterns of gene activity.

“This is a new way of regenerating adult tissue, and it has significant clinical promise for treating arthritis due to aging or injury,” senior study author Helen Blau said in a press release.

The gerozyme inhibitor “causes a dramatic regeneration of cartilage beyond that reported in response to any other drug or intervention,” senior study author Nidhi Bhutani added.

Earlier research from the same team found a molecule that’s important for the function of muscle stem cells called prostaglandin E2, which 15-PGDH breaks down.

Blocking 15-PGDH allows prostaglandin E2 levels to increase and support healing of damaged muscle, nerve, bone, liver and blood cells in young mice.

Injecting older mice with a small molecule drug designed to inhibit 15-PGDH, the knee cartilage of the animals became thicker across the surface of the joint.

Notably, the cells were also making hyaline cartilage, or smooth articular cartilage needed for healthy joint movement, with Bhutani saying the cartilage regeneration took the team by surprise and that “the effects were remarkable.”

The researchers also looked into whether the inhibitor could help recovery after a traumatic knee injury, with about 50% of people who have suffered one going on to develop osteoarthritis.

Mice that received the 15-PGDH inhibitor twice a week for four weeks saw a reduced chance of developing arthritis, compared to the untreated mice who developed it within four weeks.

Overall, the treatment appeared to push cartilage toward a younger biological state without recruiting stem cells.

Researchers also examined cartilage samples from those with osteoarthritis that was treated with the 15-PGDH inhibitor.

After one week, the tissue samples contained fewer 15-PGDH proteins, and activity associated with cartilage degradation declined, while articular cartilage regenerated.

By observing cell activity, the team’s perspective on how tissue can heal and regrow was changed.

“It’s clear that a large pool of already existing cells in cartilage are changing their gene expression patterns,” Bhutani said. “And by targeting these cells for regeneration, we may have an opportunity to have a bigger overall impact clinically.”

While the findings were limited to mouse models, an oral version of the 15-PGDH inhibitor for age-related muscle weakness exists and has been proven safe in humans.

Future clinical trials specifically testing cartilage regeneration will be needed to determine whether the treatment is safe and effective.