Cox-2 Inhibitors and Alzheimer's Disease


November 19, 1998

Doctors at the University of Rochester and 39 other medical centers around the nation have begun a research study to see if a drug known as a super-aspirin -- an investigational compound made possible by basic medical research during the last decade at the University's Medical Center -- helps prevent Alzheimer's disease.

Twenty Rochester-area patients will be part of a group of about 1,300 people nationwide who will be treated with the experimental drug, which is similar to ibuprofen, naproxen, aspirin, and other painkillers, but appears to be safer and much more efficient at squelching pain and inflammation. The first of the drugs is currently being reviewed for the treatment of arthritis and may be available next year.

The drugs target cycloxygenase-2 or cox-2, an enzyme in the body first discovered and cloned by a University team led by Don Young and Kerry O'Banion. Scientists believe the enzyme is at the root of the pain and inflammation we feel from a variety of ailments, including arthritis. Existing painkillers like ibuprofen and aspirin inhibit both cox-2 and cox-1, a closely related enzyme. For years physicians believed that knocking out cox-1 helped patients feel better, but now most doctors believe that cox-2 is the real pain-causing culprit in many illnesses. Currently drugs targeting cox-2 are being tested as a way to treat arthritis more aggressively with fewer side effects, and they're being looked at as a possible way to prevent colon cancer.

This study is one of the first to see whether such drugs might prevent or delay Alzheimer's disease. During the past few years, O'Banion and others have discovered that cox-2 is active in the brains of people who have the disease. Though the precise cause of Alzheimer's disease is still a mystery, scientists believe the enzyme plays some role in the sickness and death of brain cells of patients. Since cox-2 inhibitors muck up the enzyme's activity, they might help protect the brain against injury.

"This is a very exciting step in our efforts against Alzheimer's disease," says Pierre Tariot, a leader of the study and director of the University's Program in Neurobehavioral Therapeutics at Monroe Community Hospital, the University's main Alzheimer's treatment site. "Until now our efforts have been directed toward treating the symptoms of the disease, and as a result we have a whole series of drugs available or in development for people who have full-blown Alzheimer's."

In the study, Tariot and Anton Porsteinsson, the other principal investigator at the University, will randomly assign patients to receive either the cox-2 inhibitor Vioxx or a placebo for two years, and patients will be evaluated every few months by physicians. (Vioxx is manufactured by Merck, which is funding the $6 million nationwide study.) If the drug does work, fewer patients will develop the disease than physicians would normally expect.

"This is one of the first studies to look at possibly delaying the onset of Alzheimer's disease in people who don't have it yet but are at risk," adds Tariot. "It's remarkable that we can even consider the possibility of prevention; just 10 years ago that thought was preposterous."

CONTACT: Tom Rickey, (716) 275-7954.