Parkinson's disease: Treatment breakthrough in mice opens new path

http://dailynews.muzi.com/news/ll/en...10035633.shtml
2007-02-07

Lab mice with Parkinson's disease were able to move normally after researchers treated them with a classic anti-Parkinson's drug and a compound to slow the breakdown of naturally-occurring marijuana-style chemicals in the brain.

Mice which had been genetically engineered to have the symptoms of Parkinson's, a degenerative disease that causes trembling, jerkiness and rigidity, went from being frozen in place to moving around freely in 15 minutes after the combination treatment.

The research, led by Robert Malenka and Anatol Kreitzer of Stanford University Medical Center in California, is published on Thursday in Nature, the weekly British science journal.

"This study points to a potentially new kind of therapy for Parkinson's disease," Malenka said.

"Of course, it is a long, long way to go before this will be tested in humans, but nonetheless, we have identified a new way of potentially manipulating the (brain) circuits that are malfunctioning in this disease."

Parkinson's is linked to a depletion of a brain chemical called dopamine in a part of the brain called the substantia nigra.

As a result, less dopamine goes to the striatum, the part of the brain that helps coordinate motion.

To compensate for this shortage, patients with Parkinson's are given drugs that stimulate or mimic dopamine, although these treatments often have bad side-effects and can start to wear off after a few years.

Working on mice, Malenka's team discovered that the striatum has two distinct types of cell, each forming a circuitry that initiates motion or restrains unwanted movement.

One of the cell types turned out to have a sort of dopamine receptor -- a docking point on the cell's surface -- that the other cell did not have.

The team turned to previous work into dopamine and endocannabinoids, as the naturally-occurring marijuana-like compound is called.

Their hunch was that the two chemicals worked together to ensure smooth activation of the cell and its circuitry, which they believe inhibits unwanted movement.

They combined a dopamine mimic called quinpirole, with a new test compound, URB597, that slows the way enzymes break down endocannabinoids in the brain.

"The dopamine drug alone did a little bit but it wasn't great, and the drug that targeted the enzyme that degrades endocannabinoids basically did nothing alone," said Kreitzer.

"But when we gave the two together, the animals really improved dramatically."

Kreitzer and Malenka caution Parkinson's patients against the idea of smoking marijuana to try to achieve the same result.

They point out that their technique aims at stimulating the activity of endocannabinoids in a selected part of the brain where it occurs naturally.

This process is the opposite, and more finetuned, compared to boosting levels of endocannabinoids across the brain by smoking the drug.

According to research published in the latest issue of the journal Neurology, the number of people with Parkinson's in 15 of the world's largest nations will double, from 4.7 to 8.7 million, by 2030.

Most of the rise will be in developing countries, especially China.

Parkinson's disease is linked to old age. Thus an ageing population, coupled to greater longevity and past demographic growth, will bring a rise in the number of cases.

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