“Anyone studying Down’s is going to have their socks blown off by this,” says geneticist Roger Reeves, a Down syndrome specialist at the Johns Hopkins School of Medicine in Baltimore, who was not involved in the study. “There hasn’t been anything out there that we really could take to patients or that we had a strong possibility of taking into the clinic.”
This, in response to a new drug candidate which has been found to reduce the mental retardation associated with Down syndrome. Mouse models of Down’s syndrome (Ts65Dn mice) were given the drug, and after just two weeks performed as well as normal ones in learning and memory tests. In addition the mice’s performance increase lasted 2 months after the drug treatment ended.
So what’s this drug? A mix of three drugs: PTZ (pentylenetetrazole) + picrotoxin + a ginko bilobalide extract called bilobalide. These drugs interfere with GABA receptors and relieves inhibition between neurons, which in turn encourages new synapse formation. The Ts65Dn mice model Down syndrome by having 2 copies of chromosome 16. This results in an excessive inhibition in the dentate gyrus, which reduces synaptic plasticity; however GABA antagonists such as the drugs administered reduce that inhibition.
…clinical trials of PTZ could begin in the next year or two, and evaluating them might take five to 10 years. He notes that although PTZ is nearly 100 years old and was used to treat psychiatric disorders and later dementia, researchers never concluded it was effective. It also caused seizures (at doses 100-fold higher than those given to the mice), so the FDA revoked its approval in 1982.
Garner et al. Nature Neuroscience. Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome. Feb. 25 2007.