Thursday, January 17, 2008

A Drug for Down Syndrome

Scientists may have finally found a drug candidate for reducing the mental retardation caused by Down syndrome. After as little as two weeks on the drug, mice with a genetic impairment similar to the syndrome performed as well as normal animals did on learning tests.
The learning and memory problems characteristic of Down syndrome may occur because its sufferers' brain cells are unable to form new synaptic connections with neighboring neurons. This inhibition could be the result of overactive GABAA receptors — tiny ion channels on neurons. The drug the researchers tested, pentylenetetrazole (PTZ), interferes with the GABAA receptors, allowing new synapses to be formed at a normal rate.
For two to four weeks, researchers gave low doses of PTZ to mice bred to have an extra copy of one of their chromosomes. As in Down syndrome, this genetic anomaly causes malformed facial bones and learning problems. Immediately after treatment with PTZ, the animals' scores on two memory tests — for recognizing objects they had seen before or remembering how they last entered a maze — were on par with normal mice. Two months later the altered mice still did much better than they would have done otherwise.
The treatment 'is allowing the normal properties of neurons to work,' says Stanford University neurobiologist Craig Garner, whose group performed the experiments. 'This slowly, over time, leads to an improved circuit.'
Although the study results are hugely promising, there is a catch: PTZ, formerly used to treat psychiatric disorders, was taken off the market 25 years ago after being found to be ineffective and to cause dangerous seizures in some people. The dose used in the current study was much smaller than the dose that provoked seizures, however, so the researchers believe there is a good possibility that the drug can be used safely.
A new drug may allow children with Down syndrome to learn at the rate of their healthy peers.

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