Neuroscientists have found that a substance similar to the active ingredient in marijuana but produced naturally in the brain helps to control mobility// - and may offer a novel target for treating Parkinson's disease.
The findings by Stanford University researchers, reported in the latest issue of the journal Nature, show how marijuana-like "endocannabinoids" - one of the many chemicals used in the brain to transmit signals - form part of the neural machinery that directs normal physical movement.
A shortage of the endocannabinoids, the scientists found, can knock the system out of balance to produce the characteristic tremor, rigidity and other mobility problems of Parkinson's disease patients.
The shortage arises when another signaling system in the brain, driven by the neurotransmitter dopamine, starts to break down. Without enough dopamine, the researchers found, brain cells stop-producing endocannabinoids in the proper amount needed to control movement.
Researchers used mice specially bred so that target cells in the striatum - a region deep in the brain where endocannabinoids and dopamine operate - could be identified and recorded when the mice were given toxins to mimic the symptoms of Parkinson's. The mice were administered a drug combination - potentially a precursor of a human experimental therapy - to test the main findings.
One drug, called quinpirole, boosted dopamine - a standard medical strategy in human cases. The other drug - known as KDS-4103, being developed as a possible pain medication by an Irvine biotech company called Kadmus Pharmaceuticals Inc. - blocked the action of an enzyme that degrades endocannabinoids in the brain.
The result of this one-two punch was a dramatic improvement in Parkinson's symptoms in the mice, according to the study authors, Dr. Robert Malenka and Anatol C. Kreitzer.
"The hope is that if the same sorts of things are going on in human brains, that
maybe by using these drugs that boost levels of endocannabinoids, you will reduce the amount of dopamine drugs people have to be taking, or extend the usefulness of dopamine drugs, with less side effects," said Malenka during an interview. He was senior author of the Nature study.
If the combination proves to have a more potent effect than standard therapy in patients, "it might allow people to move better, walk better, play tennis better," Malenka added.
That would take clinical studies to prove, with the possibility of years of preclinical research to even reach the human testing stage. Independent experts said it was an intriguing new lead for a condition that afflicts 1.5 million people in the United States.
"This is an extremely intriguing finding," said Joan Samuelson, president of the Parkinson's Action Network, a patient advocacy group. "Science has been frustratingly slow in cracking the mystery of the peculiar pathology of Parkinson's."
One thing the findings in Nature don't suggest is that smoking marijuana might help alleviate Parkinson's.
Any useful therapy would have to avoid overwhelming the delicate balance of the brain's movement-control apparatus, Malenka said, boosting neurotransmitters only where they are needed.
Smoking marijuana, by contrast, floods cannabinoid receptors scattered throughout the brain with THC, the active ingredient in the plant that mimics the brain's own signaling compound. That has potent effects but there's no evidence it can help problems in the dopamine-endocannabinoid system affected by Parkinson's disease.
"When you smoke a joint, or have THC on the brain, you're activating these receptors indiscriminately, all over the place," Malenka said. "What you want is a more sophisticated and subtle perturbation of this endocannabinoid signaling system than you can get by smoking a joint."
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