Australian researchers daring to hope osteoarthritis might be treatable

Osteoarthritis cripples more than half a billion people worldwide. It's curable in mice. And maybe one day in people.

Osteoarthritis cripples more than half a billion people worldwide. It's curable in mice. And maybe one day in people. Photo: Getty

Experiments by University of Adelaide researchers suggest that osteoarthritis may be treatable. In other words, the progress of the disease could be stopped. Even reversed.

The scientists have found a novel population of stem cells they say are responsible for the progression of osteoarthritis.

In experiments with mice, this progress was reversed, and those tiny mouse joints enjoyed a “significant recovery of cartilage thickness and reduced osteoarthritis”.

What is osteoarthritis?

Osteoarthritis arises when articular cartilage – the slippery, cushioning connective tissue that facilitates ease of movement in our joints – breaks down.

It’s the crippling condition at the heart of Australia’s long waiting list for joint-replacement surgery – which doesn’t always work to eliminate or even reduce pain.

Osteoarthritis (OA) affects about 2.2 million Australians – and more than half a billion worldwide.

In 2019-2020, the disease cost the Australian health system an estimated $3.9 billion. Its progression is aggravated by ageing, obesity, injury and family history.

The new research

What’s compelling about the Adelaide research is the discovery of a “novel population of stem cells – marked by the Gremlin 1 gene – responsible for the progression of osteoarthritis”.

When treated with fibroblast growth factor 18 (think of it as a kind of fertiliser) these Gremlin 1 cells proliferated in joint cartilage in mice.

This is what led to the reported recovery of cartilage thickness and reduced osteoarthritis.

What the researcher says about it

Dr Jia Ng, from the Adelaide Medical School, co-led the study.

She said the prevailing treatments for OA are little more than a Band-Aid solution.

Where as the findings of the study “reimagine osteoarthritis not as a ‘wear and tear’ condition but as an active, and pharmaceutically reversible loss of critical articular cartilage stem cells”.

In an email to The New Daily, she writes:

“We have now painted a bull’s eye on the disease. What can we throw at it to achieve a sustainable and effective treatment to reverse the progression of osteoarthritis?”

The researchers, she said, “are now able to explore pharmaceutical options to directly target the stem cell population that is responsible for the development of articular cartilage and progression of osteoarthritis”.

All going well, said Dr Ng, patients with osteoarthritis will “no longer need to envision joint replacement in their future”.

More than one way to cure a mouse

The Adelaide researchers are not the first to claim that osteoarthritis can be effectively cured based on the success of animal studies.

Nor are they the first to claim they’ve found a novel pathway to this cure.

In 2017, John Hopkins researchers reported on mice experiments that selectively removed old or ‘senescent’ cells from their joints. This was found to “stop and even reverse the progression of osteoarthritis”.

In 2020, Stanford scientists figured out how to regrow articular cartilage by first causing slight injury to the joint tissue, then using chemical signals to steer the growth of skeletal stem cells as the injuries heal.

In 2021, Penn Medicine researchers targeted a specific protein pathway in mice, put it into overdrive and halted cartilage degeneration over time.

That’s just a sample. There are so many promising animal studies that suggest science is on the verge of a breakthrough in treating OA.

And maybe it is.

The valley of death

The big challenge, with animal studies – also known as pre-clinical studies – is making the leap across ‘the valley of death”.

This is what researchers call the difficult leap from success with animal models to success in humans.

Associate Professor Dr Julien Freitag is a Melbourne stem cell researcher and sports medicine physician.

He told The New Daily that one of the problems with osteoarthritis research in animal models is that the mice are engineered to develop an acute form of OA – which happens quickly.

In the real world, with people, OA is a slow, progressive disease.

He suggests that animal models in which mice develop OA slowly, mirroring the real world, may translate better to human experiments.

That is, they may be more successful in making the leap across the valley of death.

X-ray looks good, but symptoms get worse

Dr Freitag said there were studies, in humans with OA, where structural improvement had been achieved – lost cartilage had grown back and thickened – but the participants reported no improvement in pain and function.

“In fact, they reported that their pain had got worse,” he said. “It’s good to see a reversal in an MRI or an x-ray, but if the patients don’t feel better, you haven’t hit your goal posts.”

He said that in the “broad band of regenerative medicine, we’ve got to be mindful of what we expect to achieve, and also what is relevant to achieve. Its relevance is to improve pain and quality of life and functionality.”

Topics: Health
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