Science News

Research at Columbia University Suggests that COX-2 Inhibitors May Some Day be Instrumental in Preventing the Death of Neurons that Characterize PD

- Apr 24 2003

An enzyme that is known to cause inflammation in damaged tissues of the body, including the brain, may now be implicated in Parkinson’s, according to a new report by scientists at Columbia University in New York.

However, the researchers were surprised to find that the link was to be found not in the enzyme’s inflammatory function but in its role in a process known as oxidative stress, which is widely thought to play a role in bringing on Parkinson’s and other degenerative neurologic conditions.

The report, authored by a group of neuroscientists and led by Dr. Serge Przedborski from the Center for Parkinson’s Disease and other Movement Disorders at Columbia University, was based upon a study of the “COX-2” (cyclooxygenase-2) enzyme in mice and in samples from post-mortem human brains.

The authors found that COX-2 enzyme levels were higher in the dopamine neurons found in post-mortem brain tissue of patients who had Parkinson’s disease than in “control brains” — that is, those who did not have the disease. The loss of dopamine neurons is the hallmark of Parkinson’s.

This team of scientists found the same increased levels of COX-2 enzymes in live mice that had been treated to have a disease similar to Parkinson’s. When the animals were treated with the Rofecoxib, a COX-2 inhibitor, the number of neurons that survived doubled.

When the COX-2 was removed from mice or inhibited using the COX-2 inhibitor, surprisingly, the scientists did not see the reduction in inflammation they expected, indicating that neuron death may not be caused by inflammation. Instead, they traced the cause to oxidative stress, a process already associated with neuron death in Parkinson’s disease. They believe that COX-2 causes neuron death by oxidizing other molecules within the cell, which in turn then react with and damage other components.

Dr. Przedborski commented to the web-based resource for life sciences, www.bio.com, “Regardless of how COX-2 works in Parkinson’s disease, the benefit we see in animal models with COX-2 inhibitors suggests the drugs could be useful in slowing the disease’s progression in patients. In addition, the drugs are safe and they get into the brain reasonably well.”

He and his co-authors caution, however, that the data observed to date are very preliminary and that no conclusions should be drawn about the efficacy of the COX-2 inhibitors that are currently available. Clinical trials are needed.

A full report of the study was published recently in the Proceedings of the National Academy of Science, USA.

The study was funded, in part, by grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the U.S. Department of Defense, and the Parkinson’s Disease Foundation, New York.

Source Date: Apr 23 2003