Study finds similarities between Parkinson's disease with genetic causes and no known cause

Friday, April 28, 2006

JACKSONVILLE, Fla. — Researchers at Mayo Clinic compared patients whose Parkinson's disease stems from two known genetic causes with patients whose disease has no known cause. In both groups they found that men were affected about twice as often as women, tremor was the initial symptom in about half of all cases, and the disease almost always affected one side of the body more than the other. Dr Ryan Uitti, a Mayo Clinic neurologist and lead investigator on the study, says the findings support continued research into the genetic causes of Parkinson's disease.

Parkinson's disease is a motor system disorder that affects about 1 million Americans. The disorder is characterized by tremor, stiffness, slowness of movement and instability. It was long thought to be caused by environmental factors such as exposure to pesticides.

However, to date, researchers have discovered six genetic mutations responsible for causing Parkinson's disease in about 2 percent of all cases. They don't know what causes the remainder. "These results make studying the genetic disease even more relevant to the other 98 percent of cases we call sporadic disease," Uitti says. "Maybe there are some genetic components, or at the very least, they may share some of the same mechanisms caused by genes."

In a paper, published in the April, 2006 edition of Archives of Neurology, Uitti and his colleagues suggest that the higher incidence of Parkinson's in men is likely due to some protective effect women have rather than some environmental factor men are more exposed to. For example, the hormone estrogen may act to protect women from developing Parkinson's disease more frequently "It may be there's some other genetic influence that only women have," Uitti says. "Some other X chromosome-linked components may be playing a role."

Uitti and his colleagues previously reported that Parkinson's disease symptoms are overwhelmingly asymmetric in sporadic cases they studied. They were surprised to find the same was true in 90 percent of the patients they studied with a genetic cause. "I really thought their Parkinson's disease symptoms would be pretty much the same on both sides of the body," Uitti says. "If there's a genetic cause for a neurological problem, given the fact that genes are in every cell, in both the right side of the brain and the left side, why would there be differences in symptoms between the two sides of the body?"

Asymmetry of symptoms may have something to do with factors that determine an individual's handedness, for example. "This is an area that's completely open to speculation," Uitti says. "One thought is that this is completely hard-wired. Just like one side of the brain controls language in most people, one side of the brain creates handedness, and maybe that circuit is more vulnerable to the causes of Parkinson's disease." On the other end of the thought spectrum is the idea that overuse of a motor circuit, similar to what occurs with writer's cramp, leads to damaging the circuit and predisposing symptoms to develop on one's predominant side.

Researchers studied 40 patients from two large family kindreds with a known genetic cause of Parkinson's disease and 1277 patients diagnosed with sporadic Parkinson's disease. This series of sporadic cases, which Uitti diagnosed between July 1, 1994 and June 30, 2004, is the largest reported patient series. There are relatively few people whose genetically-caused disease resembles the disease seen in sporadic cases, but researchers say further studies involving more of these individuals is needed to assess their current findings and to discover mechanisms responsible for these common characteristics.

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