Drug restores retarded mice 'to normal'

[Lunar Loops]

This from Newsday.com:
Drug restores retarded mice 'to normal'

BY DENISE GELLENE
Los Angeles Times




February 27, 2007

Lab mice with the mental retardation of Down syndrome became smarter after being fed a drug that strengthened brain circuits involved in learning and memory, according to research reported in the journal Nature Neuroscience.

After receiving daily doses of pentylenetetrazole, or PTZ, for 17 days, the mice could recognize objects and navigate mazes as well as normal mice, researchers said. The improvements lasted up to two months after the drug was discontinued. Scientists said the study opened an avenue for research in a field that had seen little success.

"These mice are essentially restored to normal, which I haven't seen before," said David Patterson, a Down syndrome researcher at the University of Denver who was not involved in the study. "And the treatment seems to be long-lasting, which is a pretty surprising observation all by itself."

Senior study author Craig C. Garner, a Stanford School of Medicine professor, said his lab was preparing to conduct human trials of the drug.

People with Down syndrome should not be given the drug until it has been studied further, he cautioned, because PTZ can induce seizures at high doses and might have other serious side effects.

Down syndrome, a genetic disorder that occurs in 1 of 660 births, usually causes cognitive deficits, cardiac problems and physical abnormalities, such as low muscle tone, short stature and an upward slant to the eyes. More than 300,000 Americans have Down syndrome, making it the leading cause of mental retardation. There is no approved drug to improve cognition in people with Down syndrome.

PTZ blocks gamma-aminobutyric acid, or GABA, researchers said, a neurotransmitter that passes messages between neurons along specific brain pathways. Normal brains have a balance of neurotransmitters that excite neurons and make learning possible, and GABA, which slows down neurons so they do not become overly stimulated. It is believed people with Down syndrome have too much GABA, causing inhibition of brain circuits involved in learning and memory.

PTZ was used until 1982 to enhance cognition in the elderly and the mentally impaired, but it was removed from the market by the Food and Drug Administration because studies showed no clear benefits.

Garner said he believed the drug failed in part because patients adhered to a different dosing schedule from the one used in mice.

The mice were genetically altered to possess cognitive impairments similar to those of Down syndrome patients.

The mice that were fed PTZ were compared with healthy mice and untreated altered mice in tests of their mental abilities.

Researchers said it took several days for the drug to take effect. Once established, the improvements were long-lasting, but after three months the circuits in the brain showed a decline in activity, Garner said.