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News in Brief
Columbia University Medical Center researchers reported in the September 18 issue of Neurology that people with a mutation in the GBA gene (the beta-glucocerebrosidase gene, which is located on chromosome 1) have an increased risk of developing Parkinson’s disease (PD) — especially before the age of 50. The study also found that Ashkenazi Jews (those with an Eastern European background) are more likely to carry this mutation than the general population, which means this group may run a higher risk for developing the disease. An estimated 90 percent of American Jews are of Ashkenazi lineage.
Dr. Lorraine Clark, the study’s lead author, and her team performed a sequencing analysis on the GBA gene of 278 Parkinson’s patients, 178 of whom were of Jewish ancestry. They also carried out a similar study among 179 men and women without the disease.
The researchers found that 14 percent of the people with PD carried mutations in the GBA gene, while only five percent of people without the disease carried the gene mutation. The GBA gene mutation was found in 22 percent of patients who were diagnosed before the age of 50 compared to 10 percent of people whose disease onset occurred after 50.
Dr. Clark’s team then examined how Jewish ancestry affected the probability of developing PD. Of patients with Ashkenazi ancestry, 17 percent carried the GBA gene mutation, while only eight percent of patients who did not report having Ashkenazi ancestry had the abnormality.
Although the data are preliminary and it is uncertain whether the GBA mutation itself is responsible for PD or perhaps one of many contributing factors, Clark’s findings may have important implications regarding the pathology of PD that could affect future research and eventually, treatments.
Research Shows Nicotine Reduces Levodopa-Induced Dyskinesias
In the October 24 online issue of Annals of Neurology, The Parkinson’s Institute announced research findings suggesting that nicotine may have therapeutic value in easing the involuntary movements that can be a side-effect of levodopa, the gold-standard treatment for PD.
Although scientists have studied nicotine’s effects on PD before, this is the first time the tobacco ingredient’s effect on drug-induced dyskinesias has been examined.
Levodopa, the most commonly prescribed drug for Parkinson’s disease, is initially effective with few side effects, but long-term use causes dyskinesias, which are broad, writhing or jerking movements of the arms and legs.
In the study, Dr. Maryka Quik’s team administered nicotine-laced Gatorade to parkinsonian monkeys and then treated them with levodopa. The nicotine-treated monkeys experienced up to 50 percent less dyskinesias than the monkeys that were not treated with nicotine. The monkeys experienced up to 35 percent fewer dyskinesias when given nicotine after being treated with levodopa.
Given the toxicity of nicotine in high doses, researchers would have to synthesize a drug that imitates nicotine’s effects in the body, rather than using nicotine itself, in order to translate this research into treatment. The study results are exciting because they offer up a new area of research, but the topic needs significantly more investigation before leading to any potential treatment of PD.
DBS and Impulsiveness in Parkinson’s
Research published in the October 25 issue of Science has demonstrated that deep brain stimulation (DBS) may create problems of impulse control — particularly in the area of decision-making.
DBS involves placing electrodes into the subthalamic nucleus, an area of the midbrain that is important for controlling movement. It is the most commonly performed surgery for PD, and is very effective at suppressing PD-related symptoms, such as tremor and dyskinesias.
A group at the University of Arizona-Tucson, led by Dr. Michael J. Frank, studied 15 people with Parkinson’s who were taking anti-Parkinson’s medications, 17 others who had received DBS and 14 adults who did not have PD. The team used specialized computer games to test individuals’ decision-making, and to determine whether subthalamic nucleus stimulation has an impact on decision-making.
They found that the people who had DBS tended to make hasty or impulsive decisions. Whereas individuals in both other groups tended to hesitate before a decision to consider their options, those in the DBS group seemed to lose that ability to ‘slow down’ before making a decision.
It turns out that the area of the brain where DBS electrodes are implanted is the same one that plays a role in detecting conflict between choices. This area of the brain normally reacts to uncertainty by sending a signal to temporarily delay a decision for further consideration. Researchers speculate that when the DBS electrodes fire to alleviate tremor, they also block the function of the brain that causes a person to pause before making a tough decision.
Impulsivity is a potential problem in some patients with PD. More study is needed to determine the full effect of DBS on behavior and impulsivity.
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