Alzheimer's, Dementia & Mental Health
Cognitive Ability of Aging Senior Citizens May Be
Enhanced by Blood Flow Regulating Drug
Researchers speculate the stroke patient drug,
Fasudil, could reduce Alzheimers risk, improve memory, learning
Feb. 2, 2009 - A drug used to improve blood flow to
the brain also could help improve learning and memory and reduce the
risk of Alzheimer's disease for seniors, according to a new study
released today by investigators at the Translational Genomics Research
Institute (TGen) and Arizona State University.
Fasudil
has been used for more than 10 years to help protect the brain in stroke
patients by dilating blood vessels when blood flow is curtailed.
Now, a team of Arizona psychologists, geneticists
and neuroscientists report in today's edition of the journal
Behavioral Neuroscience that hydroxyfasudil, the active form of the
parent drug Fasudil, improved spatial learning (brains attempts to
interpret certain types of incoming graphical information) and working
memory in middle-aged rats when negotiating a complicated maze.
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"Fasudil shows great promise as a cognitive
enhancer during aging,'' said Dr. Heather Bimonte-Nelson, an Assistant
Professor in ASU's Department of Psychology and the paper's lead author.
"The effects in our aging-animal model were robust,
showing enhancements in both learning and two measures of memory. The
possibility that these findings may translate to benefits to human brain
health and function is very exciting."
The findings suggest that hydroxyfasudil may
influence similar cognitive processes in humans involving the
hippocampus, a part of the brain that has been shown to deteriorate in
patients with age-related disorders.
"If Fasudil proves to be safe and effective in
enhancing learning and memory, it could represent a viable new option
for the prophylactic treatment of disorders with a cognitive decline
component, said Dr. Matthew Huentelman, an Investigator in TGen's
Neurogenomics Division.
This could include diseases like Alzheimer's as
well as general age-related impairment. In short, it may be a new
pharmaceutical weapon that could be used even before the occurrence of
symptoms,"
Clinical trials are being explored in the areas of
cognitive impairment and dementia, said Huentelman, the scientific
paper's first author.
Although far from proving anything about human use
of the drug, the findings supports the scientific quest for a substance
that could treat progressive cognitive impairment, cushion the impact of
aging, or even enhance learning and memory throughout one's life span.
In the study, the researchers gave daily injections
of hydroxyfasudil to middle-aged (17-18 months old) male rats, starting
four days before behavioral testing and continuing throughout testing.
Injection made it easy to give the drug to rats, but people take it in
the form of a pill.
Rats were tested on a water radial-arm maze, which
assessed how well they remembered which of the radiating arms had a
reward, a sign of accurate spatial learning and working memory.
● Rats given a high dose (0.3750 mg per kg of
weight) of hydroxyfasudil successfully remembered more items of
information than those given a low dose (0.1875 mg per kg).
● Both dosed groups performed significantly
better than control-group rats given saline solution.
● On this same test, the high-dose group showed
the best learning (fewest total errors) and best working memory
(measured two different ways).
● For every test of learning, the scores of the
low-dose group fell between the scores of the no-dose and high-dose
groups, meaning that learning and memory boosts depended on the size of
the dose.
Fasudil, is used to protect the brain by dilating
blood vessels when blood flow is curtailed. In the body, Fasudil breaks
down into the more potent hydroxyfasudil molecule, which the authors
hypothesize may alter memory by affecting the function of a gene called
KIBRA. The authors recently demonstrated that KIBRA might play a role in
memory in healthy young and late-middle-aged humans.
Hydroxyfasudil inhibits the activity of Rho-kinase
enzymes, which have been shown to inhibit Rac, a vital protein that
supports key cellular functions. The authors speculated that blocking
Rho-kinase enables Rac, in turn, to activate more of an enzyme called
protein kinase C-zeta, which may in turn affect the KIBRA protein.
Background Informatioon
The authors received financial support from the
Evelyn F. McKnight Brain Research Foundation, the National Institute on
Aging, the National Institute of Neurological Disorders and Stroke, and
the state of Arizona.
They maintain that they have no competing financial
interests. Four of the authors hold stock in Sygnis Pharma AG, a German
pharmaceutical company that owns the rights to develop this drug class
as a potential memory enhancer. They stated that Sygnis was not directly
involved in this study, did not fund any part of it, and did not
influence the decision to study these drugs or the conclusion.
The findings appear in the February issue of
Behavioral Neuroscience, which is published by the Washington,
D.C.-based American Psychological Association.
The Translational Genomics Research Institute (TGen)
is a non-profit organization dedicated to conducting groundbreaking
research with life changing results. Research at TGen is focused on
helping patients with diseases such as cancer, neurological disorders
and diabetes. For more information, visit:
www.tgen.org.
The American Psychological Association is the
largest scientific and professional organization representing psychology
in the United States and is the world's largest association of
psychologists.
http://www.apa.org.
