Can Celebrex and Vioxx Treat Parkinson's?

Blocking a key enzyme might help slow the progression of the disease

TUESDAY, April 8, 2003 (HealthDayNews) -- Researchers have identified a brain enzyme that might contribute to the progression of Parkinson's disease.

The good news is that arthritis drugs already on the market can block the activity of the enzyme, which means the finding could lead relatively quickly to a new Parkinson's treatment.

"As a clinician, I find the results very exciting," says Dr. Jay Van Gerpen, a neurologist and specialist in movement disorders at the Ochsner Clinic Foundation who was not involved with the research. "I am cautiously optimistic this could open up real treatment options in staving off the progression of Parkinson's disease."

The study appears in this week's issue of the Proceedings of the National Academy of Sciences.

Parkinson's disease is a degenerative disorder of the brain that affects about 1 percent of Americans over age 65. Symptoms include tremors, slowness of movement and muscle stiffness to the point of paralysis.

The cause of Parkinson's is not known. However, doctors do know Parkinson's results in a gradual destruction of the neurons that transmit the neurotransmitter dopamine. Dopamine is important in regulating movement.

Certain drugs, including levodopa, can reduce symptoms of Parkinson's disease by restoring dopamine levels. But no treatment has been proven to slow the progressive cell death, Van Gerpen says. As the cells continue to die, levodopa loses its effectiveness.

"Lots of people have been looking for something that could actually slow the progression of the cell death," he says.

In the current study, researchers may be getting closer.

Researchers went looking for a particular enzyme, cyclooxygenase-2 (cox-2), in the brains of post-mortem Parkinson's patients and mice with a disease similar to Parkinson's.

Cox-2 is known to play a role in triggering the inflammation of osteoarthritis. Osteoarthritis can be effective treated with a relatively new class of drugs called cox-2 inhibitors, which help reduce the pain and swelling. These drugs include Celebrex and Vioxx, which are prescribed to people who can't tolerate aspirin or other painkillers.

Previous research had also implicated cox-2 in other neurodegenerative diseases, including Alzheimer's and amyotropic lateral sclerosis (ALS, or Lou Gehrig's disease), although the role in those diseases is not as well understood.

"Because we knew of the cox-2 inhibitors' effectiveness in treating other diseases where inflammation was a factor, and because we knew that cox-2 could somehow be involved in these other neurodegenerative diseases, we put two and two together," says Serge Przedborski, senior author of the study and a professor of neurobiology and pathology at Columbia University. "We thought it was a natural study to assess what could be the role of cox-2 in Parkinson's."

Researchers found elevated levels of cox-2 in human brains with Parkinson's, and in mice brains with a MPTP, a condition that mimics Parkinson's.

Next, researchers gave the mice cox-2 inhibitors. They found more dopaminergic neurons survived -- about 88 percent of the neurons endured while on the drug, compared to 41 percent without the drug.

But Przedborski and his colleagues were surprised when they delved further into the mechanism. They'd expected to find that cox-2 was involved with inflammation in the Parkinson's patients.

But when the mice were give cox-2 inhibitors, they saw no reduction in inflammation.

Instead, researchers believe the cox-2 enzyme may hasten cell death by causing oxidative stress, a process that causes the production of free radicals that damage surrounding cells. After enough damage, the cells die.

Previous researchers had linked Parkinson's with oxidative stress.

"There is a large body of literature supporting the idea that oxidative stress plays a role in Parkinson's, but there was nothing that showed the mechanism," Przedborski says. "Cox-2 may be involved."

The next step will be trying the cox-2 inhibitors in human trials with Parkinson's patients.

"We can argue about the intimate mechanism, but that is an issue for researchers rather than patients," he says. "The beauty of the study is that many cox-2 inhibitors are already on the market. They have a track record; they are known to be reasonably safe."

While the cox-2 inhibitors seem very promising, Przedborski said it will not be a cure.

"We've started to realize that the death of neurons is probably not the result of a single factor, but probably of multiple factors that interact with each other to ultimately kill the cell," he says.

More information

To read more about Parkinson's disease, visit the Parkinson's Disease Foundation or the National Institute of Neurological Disorders and Stroke.

SOURCES: Serge Przedborski, Ph.D., professor, neurobiology and pathology, Columbia University, New York City; Jay Van Gerpen, M.D., neurologist, Ochsner Clinic Foundation, New Orleans; April 7-11, 2003, Proceedings of the National Academy of Sciences
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