Lab mice with the mental retardation of Down syndrome got smarter after being fed a drug that strengthened brain circuits involved in learning and memory, researchers reported Sunday.
After receiving once-daily doses of pentylenetetrazole, or PTZ, for 17 days, the mice could recognize objects and navigate mazes as well as normal mice did, researchers said. The improvements lasted up to two months after the drug was discontinued, according to the report in the journal Nature Neuroscience.
Scientists said the study opened a promising 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, although he said it would take time to complete more preliminary studies and procure a supply of purified PTZ.
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 is a genetic disorder caused by an extra copy of chromosome 21. The syndrome occurs in one of 660 births and 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 a neurotransmitter called gamma-aminobutyric acid, researchers said. GABA, as it is called, passes messages between neurons along specific brain pathways. Normal brains have a balance of neurotransmitters that excite neurons and make learning possible, and of GABA, which slows neurons down so they do not become overly stimulated. It is believed that people with Down syndrome have too much GABA, inhibiting brain circuits involved in learning and memory.
The drug was used until 1982 to enhance cognition in the elderly and mentally impaired people, but 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 the dosing schedule then was different from the one his team used in mice.
