Disease Research Begins in the Unlikeliest Places
How fruit flies advance the fight against Alzheimer's disease
(HealthDay News) Medical research often involves a great deal of creativity, finding unique ways to solve challenging problems. But scientists can face skepticism when using creative methods to research human diseases, particularly when those methods involve animals or insects.
Consider the work of one research team: they are studying fruit flies to help determine the genetic causes of Alzheimer's disease.
So how can a person tell if a fruit fly is suffering from memory loss? And how would that help advance the fight against Alzheimer's?
A key expert on fruit flies, which are also called drosophila, said the connection is a fairly simple one: humans are not that much different genetically from other animals or even insects.
"Anything you can imagine that's alive can be used to study human health and disease," said Laurie Tompkins, chief of the Genetic Mechanisms Branch in the Division of Genetics and Developmental Biology at the U.S. National Institute of General Medical Sciences in Bethesda, Md.
Tompkins, who has studied fruit flies for more than a decade, noted that animals, insects, plants and even microorganisms have certain genetic and systemic similarities to humans that can be exploited by researchers to better understand human illness. "People have a hard time comprehending that a lot of the processes that go on in these organisms are similar to those in humans," she said.
For example, flies share about two-thirds of the same disease genes found in humans, she said.
"But to look at a fly, how would you know?" Tompkins added. "They look different. They behave differently. How can you tell that what's going on inside is the same?"
As it turns out, one of those genes that exist in both fruit flies and humans has been linked to the hereditary form of Alzheimer's disease, which is particularly aggressive in people, said Thomas A. Jongens, a member of the fruit fly research team and an associate professor of genetics at the University of Pennsylvania School of Medicine.
"In familial Alzheimer's, the genetics are pretty well characterized," Jongens said. "The idea is then to go and find what kind of treatments can be done to rescue and prevent this loss of memory and learning."
Jongens' research team decided to use fruit flies to test treatments that would counter the genetic mutation that causes Alzheimer's in people.
Studying the disease in flies has several advantages over studying the disease in humans:
The researchers would place a virgin male fruit fly inside a chamber with a female fruit fly that had already been mated. The male fly might try to entice the female into mating, but she would rebuff him and eventually he would stop showing interest. That lesson would overlap into the fly's next encounter: even if he were next paired with a virgin female ready for mating, his courtship behavior would be noticeably decreased.
The flies' life cycle is much shorter, only 60 to 80 days, Jongens said. A researcher can watch the onset of senility in a fly over a matter of weeks, while studying humans would take years or decades.
The flies are plentiful and provide much more research material. For example, the amount of human brain tissue available for study by Alzheimer's researchers is very limited. "You don't have available brain samples except for people who have already died," Tompkins said.
There are things researchers can do to a fruit fly that would be unacceptable on humans, including genetic manipulation to introduce the disease.
Jongens' team used a couple of unique methods related to fruit flies' courtship rituals to study memory and cognition in their subjects.
However, male fruit flies with this particular genetic propensity for Alzheimer's were unable to retain this lesson. They would keep badgering receptive and unreceptive females alike, incapable of remembering and learning that some females were not available for courtship.
The researchers gave their test subject flies drugs that theoretically would block the genetic pathways that allowed Alzheimer's to take root. Some of the drugs were experimental; one, lithium, already is approved by the U.S. Food and Drug Administration for use in humans.
The investigators found that these drugs prevented the onset of memory and learning loss in the flies, and also allowed them to recover some of their memory deficits.
"The results suggest there is a window of time when the loss of cognition is reversible through pharmacological treatment," Jongens said. "Maybe there's a window of time in human patients where these pharmacological treatments might have efficacy."
The results can't automatically be used to recommend treatment in humans. Jongens believes testing on mice is the next logical step. And after that, human clinical trials could be considered.
But the fact that lithium worked as a means of halting this form of Alzheimer's is a very hopeful finding, he said.
"One might think that would be a drug you would want to start trying immediately in humans, since it is FDA-approved," Jongens said. "It's interesting that it worked in the fly, and it suggests it should be looked at in careful studies."
On the Web
To learn more about Alzheimer's disease research, visit the Alzheimer's Association.
SOURCES: Laurie Tompkins, Ph.D., chief, Genetic Mechanisms Branch, Division of Genetics and Developmental Biology, U.S. National Institute of General Medical Sciences, Bethesda, Md.; Thomas A. Jongens, Ph.D., associate professor of genetics, University of Pennsylvania School of Medicine, and member of the fruit fly research team
Author: Dennis Thompson
Publication Date: Aug. 31, 2010
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