Retrospectacle: A Neuroscience Blog

“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.

Comments

  1. #1 steve
    February 26, 2007

    hmm… do the mice still look retarded after the drug?

    Yes, I’m going to hell.

  2. #2 Russ
    February 26, 2007

    largely for your word choice, Steve. I would have probably phrased the question “do they retain the same physical phenotype?” if I bothered spending more than a few moments on it. Unless I’m missing some deeper aspect, I would expect that neuronal antagonists would have no short term effect on facial structure or the more immutable aspects of the recipient. Otherwise identifying the users/abusers of other neuroactive chemicals would be a good deal easier.

    Back to the central focus of this… wow. If this pans out (and I’m outside of my field here) this is indeed going to blow socks off (and cause not a few tears of joy).

  3. #3 Shelley
    February 26, 2007

    No, steve, the craniofacial abnormalities wouldn’t change since those are permanent develpomental defects. The defects in the brain are not inhereantly changed either, but rather corrected chemically. I wonder if this might lead to plastic surgery to correct the facial differences?

  4. #4 Charlie (Colorado)
    February 26, 2007

    I want to know what happens if you give the same drug cocktail to normal mice.

    Sometimes I think I could use a little more neuroplasticity myself.

  5. #5 Blas
    February 26, 2007

    > I wonder if this might lead to plastic surgery to correct the facial differences?

    there are surgeries already used: tongue and eyes

    there are slso claims that nutritional supplements alleviate facial problems.

  6. #6 Ian Musgrave
    February 27, 2007

    You have mentioned it, but I’ll post this bit to emphasise it

    “But there is a catch: the drug was taken off the market 25 years ago after being found to cause dangerous seizures in some people. And many compounds that boost learning in mice fail in human trials.”

    At the moment, it looks really exciting. But lots of exciting drugs have fallen by the way (for example in Alzheimer’s disease, like the antibody that worked great in mice, but cuased dangerous inflamation in people). I really hope it does work in people though.

  7. #7 robster
    February 27, 2007

    Incredible. I’m teaching nondisjunction (as part of a meiosis unit) today, and will have to pass this along.

  8. #8 steve
    February 27, 2007

    heheh.. I know they won’t stop looking retarded don’t worry guys ;)
    just being a smartass hahaha

  9. #9 Shelley Batts
    February 27, 2007

    But lots of exciting drugs have fallen by the way (for example in Alzheimer’s disease, like the antibody that worked great in mice, but cuased dangerous inflamation in people).

    Absolutley. Only time will tell if it will be as promising in people, and whether the mouse model is as good as we think.

    …there are slso claims that nutritional supplements alleviate facial problems.

    Really? Like what?

    I want to know what happens if you give the same drug cocktail to normal mice.

    Great question. I would guess it’d be similar to an anti-ADD drug (maybe?), where some students might take it to help study or cram the night before a test. Over time though, abuse of these things can have negative effects on baseline learning and memory. So, best not to over-indulge. :)

  10. #10 dan dright
    February 28, 2007

    I’m holding off on cheering until further data supports such a specific conclusion. Looks interesting, though.

    Steve: Glad you cleared that up. Until you did, I was sure you were actually being a dumbass, smartass.

    As for an anti-ADHD medication, I would postulate rather the opposite, or no connection whatsoever. Not to mention that neural networks are very subtle interplays of inhibition and excitation, rather than monolithic on/off complexes. Or at least the poet in me would hope so.

    I’ll stick to coffee. :)

  11. #11 Russ
    February 28, 2007

    Dan,

    Just because it strikes me as a nicely snarkish comment:

    why limit yourself by employing a prefix?

  12. #12 dan dright
    February 28, 2007

    Good point, Russ, you cheeky monkey. :)