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Falling Fruit Flies Fuel Parkinson's Research

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March 22, 2000 (Atlanta) -- Falling fruit flies may be the key to a cure for Parkinson's disease, according to a study appearing in the journal Nature. Flies genetically engineered to carry a human gene linked to Parkinson's develop brain damage similar to that seen in humans with the disease. The brain damage causes the flies to literally fall off the wall of their cages.

"This is a means to rapidly screen through new drugs and get them on track quickly for human trials to help [improve] the terrible symptoms patients have," study author Mel B. Feany, MD, PhD, tells WebMD. Parkinson's disease affects about 1% of people older than 50. The symptoms -- trembling, stiffness, mask-like facial features, and a shuffling gait -- get progressively worse. This is because some as-yet-unknown process kills the brain cells that make dopamine, a substance the brain needs to work properly. Currently available drugs can ease disease symptoms for awhile, but they cannot stop the relentless course of the disease.

Parkinson's expert Robert Hauser, MD, tells WebMD that the most important clue to the disease came when it was found that patients who inherited a very rare form of Parkinson's disease had a mutated form of a common brain protein called alpha-synuclein. Most Parkinson's patients have normal forms of the protein. However, all Parkinson's patients have odd clumps in their brains that at first were thought to be dead brain cells. New research tools now show that the odd clumps are filled with tangles of alpha-synuclein. Hauser, a researcher at the University of South Florida in Tampa, says that if a drug could be found that prevented these tangles, it could cure the disease.

"We do not understand what the normal function of alpha-synuclein is and we don't know if its normal function is related to its disease function -- this points out our sad ignorance of how Parkinson's disease works," Feany says. "These are questions the fruit fly model will help us answer."

Feany and Harvard Medical School colleague Welcome W. Bender, PhD, put the human gene that produces the alpha-synuclein protein into fruit flies. The bugs remained completely normal until they reached middle age, which is day 30 of the 60-day fruit fly life span. At this point they began to act just like fruit flies dying of old age: They lost their ability to climb and began falling off the walls of their cages. When she looked at the insects' tiny brains, Feany found that they lost the same kind of cells lost during Parkinson's disease. Moreover, the brains were filled with clumps of alpha-synuclein that looked very much like those seen in humans with the disease.

Hauser, who reviewed the study for WebMD, says that the Feany experiments are at the cutting edge of research. "The breakthrough that is going to get us to the cure is the understanding that Parkinson's is a disease of abnormal alpha-synuclein [clumping]," he says. "The question is: What are the different ways alpha-synuclein can get messed up?"

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