Study Links Defective Gene to Form of Osteoarthritis : Medicine: The discovery offers hope of finding a cure for the painful condition. The potentially crippling joint disease affects millions.
In a significant step forward in the fight against one of the leading cripplers of the elderly, scientists Tuesday reported the discovery of a faulty gene that appears to cause a form of osteoarthritis, a painful and potentially disabling disease that affects millions of Americans.
Researchers at Thomas Jefferson University in Philadelphia and Case Western Reserve University in Cleveland--along with federal health officials who funded the research--announced the findings at a Bethesda, Md., press conference.
The work “provides a real clue as to why osteoarthritis may develop” and “provides real hope that curative therapy . . . will be forthcoming,” said Dr. John D. Stobo of Johns Hopkins Hospital, president of the American College of Rheumatology.
Dr. Arthur I. Grayzel of the Arthritis Foundation said the research “may change the attitude toward osteoarthritis from one of passive acceptance to a search for active intervention.”
Although the discovery is not likely to produce immediate new treatments for osteoarthritis sufferers, it promises to spur research into drugs to counteract the genetic defect, press conference participants said.
The findings are being published this month in the Proceedings of the National Academy of Sciences. A more preliminary report was published in the New England Journal of Medicine in February.
Osteoarthritis is the most common type of arthritis, or degenerative joint disease. It typically begins in early adulthood but does not generally cause problems until people are 55 or older. As the disease progresses, the cartilage that covers and cushions joints wears down and sometimes wears through, leaving a bone-on-bone joint.
It can affect many parts of the body. Men and women are affected equally. Symptoms of osteoarthritis include joint pain and stiffness. In severe cases, replacement of knee or hip joints or spinal surgery may be necessary.
The researchers focused on a form of osteoarthritis that strikes earlier than usual--as early as the second or third decade of life--and is inherited. They studied 19 members of a three-generation family, nine who have osteoarthritis and 10 who don’t.
The researchers used sophisticated techniques of DNA and protein analysis to identify the faulty gene. The gene they targeted directs the body to produce a protein known as type II collagen, which strengthens cartilage.
They discovered a defect in the type II procollagen gene. The defect causes one amino acid, cysteine, to be erroneously placed in the collagen protein, which is composed of more than 1,000 amino acids. The amino acid substitution helps to destabilize cartilage.
The defective gene was found in all nine family members who suffered from osteoarthritis but not in any of the unaffected members or in 57 unrelated individuals who were tested. The relationship between this early-onset form of osteoarthritis and the more usual form is not entirely clear.
The authors of the study believe that the more common form of the disease may result from the same faulty gene or other genetic defects that have yet to be discovered. They called it a myth to look at osteoarthritis as an aging disorder.
Dr. Darwin J. Prockop of Jefferson Medical College, one of the lead researchers in the study, said the team decided about four years ago to look for a genetic cause to explain why cartilage falls apart in osteoarthritis.
Current treatments for osteoarthritis vary with the severity of the disease. They range from patient education and exercise to anti-inflammatory drugs and steroid injections and surgery.
Steinbrook reported from Los Angeles and Cimons from Washington.
