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Novartis Compound Spurs Cartilage in Arthritic Mice

Scientists at Novartis AG (NOVN) have discovered a compound that spurred cartilage growth from stem cells to fix damaged joints of mice, a finding that may point to a novel therapy for the arthritis that afflicts most elderly.

Researchers tested 22,000 drug-like molecules using a robotic screen, applying each one to bone marrow stem cells in tiny laboratory dishes. One compound, dubbed kartogenin, promoted the development of chondrocytes, cells that become cartilage, according to the report in the journal Science.

Researchers injected kartogenin into the damaged knee joints of mice, which prompted cartilage regeneration, improved symptoms and lowered levels of proteins and collagen fragments linked to damaged joints. The results suggest a unique, though early-stage, way to regulate cartilage and possibly repair some of the damage from osteoarthritis, the breakdown of cartilage that leads to joint failure, the researchers said.

“We found this molecule that can take stem cells that are already in the joint, and differentiate them into chondrocytes,” cartilage cells that secrete the squishy elastic substance that protects the joints, said Kristen Johnson, a regenerative medicine researcher at the Genomics Institute of the Novartis Research Foundation in San Diego. “We’re excited about the biology because it’s a new way of targeting the stem cells, but you can’t emphasize enough what an early stage of drug discovery this is.”

Additional work is needed to understand exactly how kartogenin works and the basic biology it affects before more animal studies are done, said Johnson, who is also part of the Novartis Institutes for BioMedical Research. Novartis is based in Basel, Switzerland.

Pain and Surgery

The only current treatments for arthritis, which affects 50 percent of 50-year-olds, 60 percent of 60-year-olds and so on, are pain management and surgery, said Johnson.

Osteoarthritis is called the “wear-and-tear” form of the disease. It develops when the cartilage that protects the joints wears away, allowing the bones to rub against each other. Each year, there are more than 600,000 total knee replacements and 285,000 hip replacements done in the U.S. because of arthritis and other injuries, according to the Agency for Healthcare Research and Quality.

The mouse studies didn’t turn up side effects from the treatment, though only small quantities were injected directly into the joint, Johnson said. Taken together, the laboratory and animal work suggests that steering adult stem cells into becoming new cartilage leads to improvements in the damaged joints when given early in the disease, researchers said.

The California Institute for Regenerative Medicine funded the research. The researchers, including Johnson and colleagues from The Scripps Research Institute in La Jolla, California and Massachusetts General Hospital in Boston, filed for a patent.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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