Infinity Group Medical Director Dr Krish Rawal, shines light on Osteoarthritis and possible medical advances in the future.

Now we are all getting back in to our training regimes, I am sure some of us (me included) are complaining about our aching, creaking knees.

Did you know that Osteoarthritis (OA) remains a leading cause of disability worldwide, largely because articular cartilage has very little intrinsic regenerative capacity and, unfortunately no disease-modifying medications currently exist. Recent preclinical research has discovered that inhibiting 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme that increases with ageing and joint injury, has potential as a new regenerative treatment. 15-PGDH breaks down prostaglandin E₂ (PGE₂) which is a key mediator of tissue repair. In some test environments, both systemic and intra-articular administration of a small-molecule 15-PGDH inhibitor restored the levels of PGE₂, leading to significant regeneration of articular cartilage, reduction in OA associated pain, and improved joint function.

This amazing regenerative response was observed in two clinically relevant contexts: age-related cartilage loss and post-traumatic Osteoarthritis. In aged mice, previously thinned cartilage increased in thickness and structural integrity, while in injury models, such as those mimicking an anterior cruciate ligament rupture, treatment markedly reduced the development of OA compared with controls. Functionally test subjects demonstrated more normal weight-bearing and better mobility. At the cellular level, cartilage cells (chondrocytes) exposed to the inhibitor showed restoration of cell function and early re-establishment of cartilage characteristics.

Translating that to human subjects: osteoarthritic cartilage obtained during knee surgery showed suppressed degenerative gene programmes and early regenerative changes after only one week of exposure to the inhibitor. The good news is that oral formulations of 15-PGDH inhibitors are already in early-phase clinical trials for other age-related conditions to support the case for introducing this new treatment to mainstream medicine. While these findings remain preclinical for Osteoarthritis, they represent a major shift toward “regenerative pharmacology” without stem-cell implantation or prosthetic joint replacement, targeting a master regulator of age-related tissue decline. If replicated in clinical trials, this approach could be transformational for Osteoarthritis management and for my knees!