From foodconsumer.org
Old drug may help Down syndrome patients
By Ben Wasserman - foodconsumer.org
Feb 25, 2007 - 5:46:54 PM
If you like the article, could you please do us a favor? Just tell Google News Services that you like foodconsumer.org included in Google News Services. Inclusion in googlenewsservices means many more people can read articles like this. Thanks.
------
A once-thought-to-be-useless
compound turns out to be a promising agent that may be used to improve learning ability
and memory in children with Down syndrome, according to a new study published
Feb. 25 in the advance online edition of
Nature Neuroscience.
The study found that
mice with Down syndrome symptoms that received a short term daily treatment of
pentylenetetrazole, or PT improved their memory and learning ability.
Better yet, the
researchers from the Stanford University School of Medicine and Lucile Packard
Children's Hospital found the positive effect lasted for months after the
treatment was discontinued.
The researchers are
planning to continue their study in clinical trials to test if PTZ has the same
or similar effect in humans with Down syndrome.
"This treatment
has remarkable potential," said Craig Garner, PhD, professor of psychiatry
and behavioral sciences and co-director of Stanford's Down Syndrome Research
Center, which was created by researchers at Stanford and Packard Children's
Hospital in 2003 to develop useful treatment based on current research
discoveries for people with Down syndrome.
"So many other
drugs have been tried that had no effect all. Our findings clearly open a new
avenue for considering how cognitive dysfunction in individuals with Down
syndrome might be treated," Garner added.
In the study, Fabian
Fernandez, a graduate student in Garner's laboratory, found that after being
fed milk containing a low dose of PTZ daily for 17 days, affected mice were
much better than ever at identifying novel objects and navigating a maze task
that simulated difficulties experienced by patients with Down syndrome.
The mice receiving the
PTZ treatment performed just as well as their wild-type counterparts for months
even after the treatment was discontinued, according to the researchers.
"Somehow the drug
treatment creates a new capacity for learning," said Garner, who cautioned
that the effect is not fixed and the newly gained ability may disappear over a
period of time as the drug-influenced neurons are replaced by new cells.
The researchers hypothesized
that the improvement was achieved because PTZ blocks the action of an
inhibitory neurotransmitter called GABA. Normal brains function in a way that
it keeps a balance between neuronal excitation and inhibition to allow
efficient learning.
By the researchers'
account, the Down syndrome patients have too much GABA-related inhibition,
which as a result makes it hard for the brains to function normally.
"In general,
learning involves neuronal excitation in certain parts of the brain," said
Garner. "For example, caffeine, which is a stimulant, can make us more
attentive and aware, and enhance learning. Conversely, alcohol or sedatives
impair our ability to learn."
The study was
conducted in a mouse model of Down syndrome in which about 150 genes were
triplicated and many cognitive problems the mice suffered also inflict people
with Down syndrome.
The researchers tested
PTZ in mice with Down syndrome to see how they perform when subject to unfamiliar
objects and a T-shape maze.
In the first test,
mice were exposed to two similarly sized, yet different objects for 15 minutes.
Then 24 hours later, they were exposed to one of the previously seen object and
a third new object.
Wild mice spent more
time studying the new object while the untreated mice with Down syndrome mice
did not show any preference for either object.
In the T shape maze
test, mice were first habituated to the long arm of a T-shaped maze and then
allowed to explore. Wild-type mice tended to study first one, then the other
arm of the maze. In comparison, untreated Down syndrome mice were less
methodical.
However, the mice with
Down syndrome performed more like the wild-type on both types of tests after a
17-day treatment of PTZ.
Garner and Fernandez
discovered that PTZ had to be used for several days until the effect could be
detected. But once detected, the effect lasted for up to two months. In a
sense, the researchers said the drug's activity profile is similar to that of
some well-known psychiatric medications.
"This suggests
that it's not just the removal of the excess inhibition that allows learning to
occur, but that we're instead strengthening synapses through some type of
long-lasting neuronal adaptation," said Garner.
Mice with Down
syndrome lacked long term potentiation that needed to be achieved to make the neurons
sensitive to excitation, explained Postdoctoral scholar Wade Morishita, PhD,
who works in the Stanford laboratory of Professor Rob Malenka, PhD.
Morishita found that chronic
treatment of PTZ helped achieve the long term potentiation that made the Drown
syndrome mice perform as well as wild-type mice for up to three months after
the treatment was discontinued.
Garner and Fernandez said
PTZ
’
s history of use in humans could make it easier
for researchers to start human trials. But
they strongly cautioned individuals against using PTZ or other similar
compounds on their own to treat Down syndrome.
Use of PTZ in humans
can only be allowed after trials demonstrate that the drug is effective and
safe.
The researchers also cautioned that
the drug did not help normal mice with their learning capabilities.
"We
’
re not in the business of cognitive
enhancement," said Fernandez. "Basically, we have something that
could be one part of the many different medical and environmental interventions
that may allow kids with Down syndrome to live more normally."
In addition, PTZ
should not be used at high doses though as the study authors cautioned that
just as what high doses of caffeine can do to the body, so does PTZ. High doses
of PTZ can cause seizure.
In fact, PTZ has been
primarily used for the study of epilepsy in animals after some brief,
inconclusive studies conducted in elderly or mentally impaired people in the
1950s.
Epilepsy (sometimes
referred to as a seizure disorder) is a common chronic neurological condition
that is characterized by recurrent unprovoked epileptic seizures, according to
wikipedia.com
PTZ has not been
approved by the Food and Drug Administration for any treatment since its withdrawal
in 1982 when the agency found the drug does not have any clear clinical
benefit.
"My idea was that
it might be possible to harness this excitation effect, which at higher doses
can be pathological, to benefit people with Down syndrome," said
Fernandez.
Dow syndrome, the
leading cause of mental retardation, affects more than 300,000 people
nationwide in the
U.S.
About 5,000 children are born with Down
syndrome in the United States each year.
The condition is caused by an extra copy of
chromosome 21. Children with this condition have high risk of heart disease,
leukemia and early onset Alzheimer’s disease.
For more information about Down syndrome, visit Facts about Down Syndrome.
##