Injectable Drug Reprograms Cells to Regenerate Cartilage and Prevent Arthritis

Researchers from Stanford Medicine announced in November an injection that can reprogram cells to regrow cartilage and help prevent arthritis from developing. The treatment represents the first drug that may treat cartilage loss, offering a new approach to regenerating adult tissue with significant clinical promise for treating arthritis due to aging or injury.

The researchers targeted one of the root causes of osteoarthritis: a protein called 15-PGDH. The team previously identified 15-PGDH as a gerozyme—or a master aging regulator—that degrades prostaglandin E2, which is essential for muscle stem cell function. Through their research, they discovered that levels of the protein increase significantly with age. When they tried blocking the protein, they saw increases in the muscle mass and endurance of older mice. Their findings were further affirmed when they found that dosing young, healthy mice with 15-PGDH actually shrank their muscles.

The researchers then focused specifically on the cartilage itself. They injected the mice with a small molecule drug, experimenting with location. Some mice received the injection into their abdomen, which would theoretically affect the whole body, and the researchers injected others directly into their joints. Both administration methods resulted in knee cartilage thickening. Through this treatment, researchers managed to turn back the clock on chondrocytes—or the cells found in cartilage—encouraging them to assume a more youthful state and produce functional cartilage, no stem cells needed.

The director of the Baxter Laboratory for Stem Cell Biology at Stanford stated in a press release: "We were looking for stem cells, but they are clearly not involved. It's very exciting." The senior author of the paper, published in the journal Science, noted that cartilage regeneration to such an extent in aged mice took the team by surprise, calling the effect remarkable.

Beyond age-related joint pain, the therapy could address osteoarthritis caused by injuries, including ACL tears, which are common among athletes in high-impact sports. The condition occurs in up to 87 percent of patients with previous ACL injuries, according to some estimates. The Stanford research team found that two injections a week across a four week window significantly reduced the likelihood of mice developing osteoarthritis.

There have already been successful Phase 1 clinical trials for an oral version of the 15-PGDH inhibitor, testing the drug's effect on muscle weakness. The researchers hope to run a similar trial to fully understand the injection's promise for cartilage regeneration. The director of the Baxter Laboratory stated: "We are very excited about this potential breakthrough. Imagine regrowing existing cartilage and avoiding joint replacement."