The situation is an increasingly urgent medical concern; 50,000 more Americans are diagnosed with Parkinson’s each year. Parkinson’s disease patients have trouble with movement. They move slowly. They have rigidity in their limbs. They have balance problems and tremors.
These cardinal symptoms are a result of a deficit of dopamine in the brain.
Dopamine is a neurotransmitter that’s essential for movement; it also plays an important role in behavior, cognition and sleep.
In Parkinson’s patients, neurons that make dopamine die. Scientists still aren’t sure why; genetic factors are believed to play only a small role.
The situation is an increasingly urgent medical concern; 50,000 more Americans are diagnosed with Parkinson’s each year . This deficit of dopamine can be reversed with treatment using a compound called L-DOPA.
The brain converts L-DOPA into dopamine, which is why it’s an effective replacement therapy for patients. And for five to 10 years, this treatment works well.
“The problem is that Parkinson’s is a progressive disease,” said Bishop, assistant professor of psychology at Binghamton University. “You lose more and more of these neurons as time goes on, so therapeutically, doses of L-DOPA must increase.”
Many patients suffer troubling side effects as the dosage increases. “By year 10,” Bishop said, “as many as 90 percent of patients will start to suffer from motor fluctuations and something called L-DOPA-induced dyskinesia. So you go from a state of no treatment where you’re not moving well, to a state where the drug is working well and you’re moving fluidly, to a point where L-DOPA doses are very high and you’re producing these abnormal, involuntary movements.”
Think of the actor Michael J. Fox’s recent television appearances. The excessive movements he displays aren’t a result of his Parkinson’s disease, but rather a symptom of the L-DOPA therapy.
“It’s this inability to suppress movement that’s a real problem for patients later on in the disease’s progression,” Bishop said.
And patients can’t simply stop taking L-DOPA, Bishop said. If they do, they face a nearly “frozen” life with incredibly limited ability to move.
It’s unusual that there hasn’t been a change in the primary treatment for Parkinson’s in five decades, Bishop said. In that time, there have been huge advancements in the ways other neurologic disorders are treated.
With Parkinson’s, there are still a number of big unanswered questions. The cause of the disease is one; how dyskinesia develops is another.
Bishop and colleagues at Wayne State University’s medical school and the Veterans Administration hospital in Chicago hope to find a way to reduce dyskinesia and suppress these movements.
“We’re asking, ‘Is dyskinesia abnormal learning?’ There are parts of the brain that allow us to store memories. And that involves laying down new neuronal pathways that become permanent. You can now go and retrieve that information.
It’s not always at the forefront of your mind, but it’s something you can get to if you need to,” Bishop said. “In the same way, your ability to produce a movement is a memory. It’s a motor memory, but it’s a memory nonetheless.
“We are beginning to believe that dyskinesia is actually the inability to suppress motor memories as a result of the drug’s stimulation. These abnormal movements may be an expression of motor memories that can’t be shut down.”
One possible treatment relates to glutamate, a neurotransmitter in the brain that can play a role in these memory processes, helping to lay down new pathways for motor memories.
Bishop has developed a way to look at dyskinesia as it’s occurring and measure glutamate levels in different parts of the brain. “That is a huge leap forward,” he said, “because now we can make an association between the behavior and the glutamate levels. And we’re doing it in a very specific area of the brain. It’s a very powerful technique.”
Kathy Steece-Collier, an associate professor in the Department of Neurology at the University of Cincinnati, said “surprisingly little” research effort to date has taken the direction Bishop is pursuing.
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