Stanford blocks aging protein to regrow cartilage in
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- Stanford Medicine researchers restored lost knee cartilage in old mice using a small-molecule drug that blocks the aging-related protein 15-PGDH, with regenerated tissue confirmed as the hyaline cartilage type needed for healthy joint function.
- In a mouse model of ACL tears, mice given the 15-PGDH inhibitor twice weekly for four weeks were far less likely to develop osteoarthritis, while untreated mice developed the disease within four weeks and had roughly double the 15-PGDH levels of uninjured animals.
- Cartilage samples collected during human knee replacement surgeries began producing new articular cartilage after one week of exposure to the treatment, with fewer cartilage-degrading cells and lower activity of breakdown-linked genes.
- Unlike most regenerating tissues, cartilage repair here did not rely on stem cells — chondrocytes instead shifted their gene expression back toward a more youthful state, with hyaline-cartilage-building cells rising from 22% to 42% of the population.
- Senior authors Helen Blau and Nidhi Bhutani say the approach could be delivered as a knee injection or oral medication, and noted that an oral 15-PGDH inhibitor is already in Phase 1 trials for age-related muscle weakness, where it has shown safety in healthy volunteers.
- The study targets osteoarthritis — which affects roughly one in five US adults and generates an estimated $65 billion in direct annual healthcare costs — and is the first drug approach shown to regrow cartilage in this way, published in Science.
Why it matters: The approach could reduce the need for knee and hip replacements, currently the only option for end-stage disease in the one in five US adults with osteoarthritis, generating $65 billion in annual direct costs. Phase 1 safety data from the existing muscle-weakness trial gives the cartilage program a head start on human testing.
