Parkinson's Tremors (06.21.05) - Using tiny technology, UCLA engineers have developed devices that may offer insight into exactly how one kind of treatment is so successful in relieving tremors in some Parkinson's patients.
An illegal drug that's notorious for its use in nightclubs may one day help keep Parkinson's disease patients on their feet. As this ScienCentral News video explains, an animal study suggests ecstasy might ease Parkinson's-related decline.
Ecstasy to Ease Parkinson's Disease
Disease nosed its way into David Eger's life gradually. At first, he couldn't raise his elbow as high as usual. He brushed it off as a possible gym injury. But soon, his left fist would clench and go rigid.
"My family began to notice it and observe it, so I decided I'd better go and have somebody look at it," says Eger, a 60-year old clinical psychologist. After testing, Eger's was diagnosed with Parksinson's disease, a brain disorder that whittles away the brain's ability to make a key chemical called dopamine that controls body movement.
Now, researchers working on a study in mice have found that a popular dance club drug — the amphetamine, ecstasy — might help patients like Eger combat the physical decline that accompanies Parkinson's.
"We went and tested as many as 70 drugs total, belonging to 20 different pharmacological groups," explains Raul Gainetdinov, a neuroscientist who was part of the Duke University team that studied the effects of amphetamines in lab mice that have Parkinson's-like symptoms. "To our surprise, not many things really worked. When we tried with ecstasy it was the first drug that we discovered working... It was amazingly effective," he says. "[The mice] went from a situation where they were completely frozen to ability to move quite a significant distance, and pretty much normally."
As reported in Discover Magazine, the researchers studied genetically engineered mice that produce almost no dopamine, a brain neurotransmitter. The dopamine the mice do produce is on a moment-to-moment basis, unlike the constant dopamine production we need to keep our brain functioning properly.
Gainetdinov, and the study's lead author, Marc Caron, gave these mice chemicals that eliminated production completely, so that the mice had a total absence of dopamine.
"Within about a half an hour to an hour... these animals [show the symptoms of Parkinson's]," says Caron. "They're rigid. They can't initiate movement. They have some tremor. And these symptoms can last anywhere from six to eight hours. After that, the drug wears off and they become normal. But during that time you can actually test other drugs [on them] and this is when we tested all these various classes of drugs."
Since prior studies had already shown that ecstasy can help with Parkinson's symptoms, the team tested it on the mice. What the researchers say is surprising about their study, Caron explains, is that, "Amphetamines are believed to work almost totally through increasing the concentration of dopamine in the brain. These animals cannot increase the concentration of dopamine because there is no dopamine to be measured. So, the fact that these amphetamines were active suggests that they may be working by other mechanism."
The researchers don't know what that mechanism might be, but Caron says he has a hunch: "Recently, there's been a class of receptor that's been discovered which are called trace amine receptors. So, these are receptors that are very much like the receptors that we have in the brain that mediate the action of dopamine… but we didn't know before that these receptors existed in the brain. It's been shown in cell studies… that amphetamines are actually good compounds to activate these receptors. So, the theory that we have is that possibly these amphetamines may be working through these mechanism."
Gainetdinov says the next step is to test Caron's theory, but adds that there could be a more immediate use for the team's current findings. Right now, the most effective drug to treat Parkinson's disease is L-dopa. But L-dopa has long-term side effects. Patients can lose complete control of their muscles — a symptom called dyskinesia — and as time goes by they require more and more L-dopa to get the same therapeutic effects it once gave them.
By mixing L-dopa with amphetamine compounds, Caron and Gainetdinov found that they could reduce the amount of L-dopa given to the mice without losing the dramatic movement the mice gained. Says Caron, "You can use a much lower concentration of L-dopa. Then, that might do away with some of the side effects of L-dopa treatment, which is dyskinesia and complications such as these." But they stress that in no way do they want their research to be taken as a sign that it's okay to self-medicate with amphetamines.
Michael Hutchinson, a neurologist at NYU Medical Center, also studies Parkinson's. He says the Duke findings will need some repeating but that treatment with amphetamines could be promising."What is interesting about this paper is that in the absence of dopamine… in this model of the end stages of Parkinson's, where no known drug is particularly effective, these amphetamine compounds will reduce the signs and symptoms of Parkinson's in the animal," he says. "This suggests that they might be useful for the later stages of Parkinson's where conventional medications fail to work."
David Eger says he keeps an eye peeled on current Parkinson's research, and as a member of a patient advisory board on Parkinson's for the Federal Drug Administration, he meets with leading experts to advise them on how Parkinson's impacts the lives of ordinary people.
So far, Eger's physical decline has been slow and not completely disruptive of the active life he still enjoys, which includes working out four to five times a week at the gym. In a way, he says, Parkinson's has opened a new world for him because of the Parkinson's patients and advocates that he meets, "It sounds funny I suppose, but there is a way in which I feel very grateful for that," he says.