A combination of two previously studied osteoarthritis drugs reverses arthritis in rats

The top image shows a knee joint in a healthy rat. (White indicates cartilage.) The second image from top shows a joint with grade 2 untreated osteoarthritis. The third image shows a joint with osteoarthritis that has worsened from grade 2 to grade 4 after six weeks of placebo therapy. The bottom image shows a joint with osteoarthritis that improved from grade 2 to grade 1 (mild) after six weeks of combination therapy with alphaKlotho and sTGFbR2. Credit: Salk Institute

The top image shows a knee joint in a healthy rat. (White indicates cartilage.) The second image from top shows a joint with grade 2 untreated osteoarthritis. The third image shows a joint with osteoarthritis that has worsened from grade 2 to grade 4 after six weeks of placebo therapy. The bottom image shows a joint with osteoarthritis that improved from grade 2 to grade 1 (mild) after six weeks of combination therapy with alphaKlotho and sTGFbR2.

Credit: Salk Institute

Article Highlights
  • People with osteoarthritis, or “wear and tear” arthritis, have limited treatment options: pain relievers or joint replacement surgery. Now, Salk researchers have discovered that a powerful combination of two experimental drugs reverses the cellular and molecular signs of osteoarthritis in rats as well as in isolated human cartilage cells
  • “What’s really exciting is that this is potentially a therapy that can be translated to the clinic quite easily,” says Juan Carlos Izpisua Belmonte, lead author and a professor in Salk’s Gene Expression Laboratory. “We are excited to continue refining this promising combination therapy for human use.”
  • Affecting 30 million adults, osteoarthritis is the most common joint disorder in the United States and its prevalence is expected to rise in coming years due to the aging population and increasing rate of obesity. The disease is caused by gradual changes to cartilage that cushions bones and joints. During aging and repetitive stress, molecules and genes in the cells of this articular cartilage change, eventually leading to the breakdown of the cartilage and the overgrowth of underlying bone, causing chronic pain and stiffness
  • The researchers treated young, otherwise healthy rats with osteoarthritis with viral particles containing the DNA instructions for making αKLOTHO and TGFβR2
  • Six weeks after the treatment, rats that had received control particles had more severe osteoarthritis in their knees, with the disease progressing from stage 2 to stage 4. However, rats that had received particles containing αKLOTHO and TGFβR2 DNA showed recovery of their cartilage: the cartilage was thicker, fewer cells were dying, and actively proliferating cells were present. These animals’ disease improved from stage 2 to stage 1, a mild form of osteoarthritis, and no negative side effects were observed
  • “From the very first time we tested this drug combination on just a few animals, we saw a huge improvement,” says Isabel Guillen-Guillen, also a Salk postdoctoral fellow and the paper’s co-first author. “We kept checking more animals and seeing the same encouraging results.”
  • “We think that this could be a viable treatment for osteoarthritis in humans,” says Pedro Guillen, director of the Clinica CEMTRO and co-corresponding author

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