Osteoarthritis: cartilage can regenerate – the ‘switch’ for regrowth has been discovered

Could simply ‘switching off’ an enzyme be enough to repair joints worn down by time? A study published in Science by researchers at Stanford University (California, USA) suggests a potentially revolutionary solution to osteoarthritis. The results are surprising, although for now they are based on experiments on mice and human tissues studied in the laboratory. Meanwhile, however, the pipeline of 15-PGDH inhibitors is making rapid progress, thanks to a biotechnology company, Epirium Bio, which has acquired a spin-off from Stanford University, co-founded by Dr Helen M. Blau, author of this research published in *Science*.

A knee worn down by osteoarthritis that starts producing cartilage again. A damaged joint that, rather than continuing to deteriorate inexorably, begins to repair itself. And, in the long term, the possibility of postponing – or perhaps even avoiding – the need for a joint replacement. It sounds like science fiction, but this is the scenario opened up by research from Stanford University, published in the prestigious journal *Science*. American scientists have identified a sort of molecular switch which, once switched ‘off’, appears to restore the cartilage’s capacity for regeneration – a capacity previously thought to be extremely limited. A potentially revolutionary discovery for millions of people struggling with osteoarthritis. But let us proceed with caution: we are still at the preclinical stage, not on the very eve of a revolutionary cure.

The enemy of cartilage now has a name: 15-PGDH. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is an enzyme that contributes to the breakdown of prostaglandins, molecules involved in numerous biological processes. Its activity increases with ageing and can hinder tissue repair mechanisms. Researchers at Stanford have attempted to block it, achieving a surprising result: in ‘elderly’ mice, the inhibition of 15-PGDH promoted the formation of new articular cartilage. Furthermore, in experimental models of osteoarthritis, benefits were also observed in terms of cartilage damage and pain.

The most interesting development is that this ‘regeneration’ process does not require the use of stem cells. When this molecular switch is turned off, it is the chondrocytes themselves – that is, the cells already present in the cartilage – that spring into action, altering their biological programme and resuming the production of components of the cartilage matrix. In other words, it is not a matter of implanting new cells, but of ‘persuading’ the existing ones to undertake a reparative process.

But what stage have human trials reached? American scientists have also studied samples of human cartilage taken from patients who had undergone knee replacement surgery. Inhibition of 15-PGDH stimulated responses consistent with increased regenerative activity in these tissues as well. This is an important finding, as it suggests that the mechanism identified in mice may also be relevant to the biology of human cartilage. Of course, it is one thing to observe a response in the laboratory; it is quite another to demonstrate that a drug can regenerate articular cartilage in a person, provide lasting pain relief and delay or prevent the need for surgery.