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Phenserine
Shows Potential To Slow Or Stop Progression Of Alzheimer's Disease
The Gila monster — a native lizard to
the southwest United States and Mexico — can be deadly but its saliva
also contains a chemical which acts on a previously unknown receptor
pathway in the brain that affects memory.
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SeniorJoural.com readers can listen to an audio replay of a
telephone news conference on this announcement by dialing
1-800-428-6051 using this pass code - 236493 - through April 12.
• To learn
more about Phenserine research by Axonyx -
Click Here
• To learn
more about Alzheimer's Research by Axonyx -
Click Here |
April 4, 2002 -
Results reported in an abstract on the transgenic mouse confirmed that
Phenserine, a third generation acetylcholinesterase inhibitor (AChE-inhibitor),
has the ability to reduce both amyloid precursor protein (APP) and
amyloid peptide (amyloid-beta) formation in the brain which could have
important potential implications for the treatment of Alzheimer's
Disease (AD).
Dr. Nigel Greig of
the National Institute on Aging/National Institutes of Health (NIA/NIH),
together with collaborators that included Dr. Debomoy Lahiri (Indiana
University School of Medicine) and Dr. Kumar Sambamurti, presented
data in a poster session today, entitled "Amyloid-Modifying Properties
of The Acetylcholinesterase Inhibitor, Phenserine," at The 7th
International Geneva/Springfield Symposium on Advances in Alzheimer
Therapy, April 3 - 6, 2002 in Geneva.
"Unlike other
acetylcholinesterase inhibitors that simply suppress the activity of
the enzyme, Phenserine's dual mechanism of action, to reduce amyloid-beta
levels via its actions on APP, suggests that it not only has the
potential to improve memory and cognition, but also to slow the
progression of the disease," reported Drs. Greig, Lahiri, Sambamurti
and colleagues.
The neurotoxic
peptide, amyloid-beta, that is the core constituent of the plaques
found in the AD brain, is generated by the proteolytic cleavage of APP
by a group of enzymes whose inhibition is a strategy for AD treatment.
Significantly however, and unassociated with its acetylcholinesterase
action, phenserine reduces the synthesis of APP to a level that
retains its physiological function but that reduces the amyloid-beta
derived from it. Lowering amyloid-beta levels is achieved without
affecting APP proteolytic enzymes, which are reported to possess other
critical functions. Reducing amyloid-beta formation and its resulting
deposition could favorably modify AD progression.
Study Results
The objective of
the research was to determine the effect of Phenserine on the levels
of APP and amyloid-beta in tissue culture and assess whether or not
tissue culture results translated to an in vivo transgenic mouse
model. Double transgenic mice that over-express human APP and amyloid-beta
were treated with either saline or phenserine for three weeks.
Thereafter, brain and cerebral-spinal fluid (CSF) levels of APP and
brain levels of amyloid-beta were quantified and compared.
The results of
the study indicate that Phenserine:
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Reduced APP and amyloid-beta levels
in neural cells in tissue culture: This occurred by reducing APP
synthesis rate via a post-transcriptional mechanism.
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Reduced APP in transgenic mice:
Compared to controls, Phenserine reduced APP levels by 10% (p<0.05)
in cerebral cortex and 55% (p<0.05) in CSF.
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Reduced amyloid-beta in transgenic
mice: Levels of amyloid-beta were reduced by in excess of 50%.
This study
confirms and extends research announced last year by Drs. Greig,
Lahiri, Sambamurti and colleagues in the "Proceedings of the National
Academy of Sciences [2001 Jun19:98(13):7605-10]" highlighting
Phenserine's ability to inhibit the formation of APP and amyloid-beta
in tissue culture and defining the mechanism involved.
"Scientists are
now acknowledging that Alzheimer's Disease involves a complexity of
connected cascade-like events," stated Marvin S. Hausman, M.D.,
President and CEO, Axonyx Inc. "Phenserine's novel dual mechanism of
action has the potential to usher in a different therapeutic approach
to controlling this tragic disease."
A Highly
Selective Acetylcholinesterase Inhibitor
Phenserine
represents the next generation of AChE inhibitors, as indicated by its
unique pharmacodynamic and pharmacokinetic profiles. It is a potent
and selective inhibitor of acetylcholinesterase, an enzyme that breaks
down the critical neurotransmitter acetylcholine that is involved in
memory and cognition but is deficient in the AD brain. In pre-clinical
studies, Phenserine demonstrated a brain-to-blood ratio of 10:1. These
properties could potentially maximize the therapeutic effects of the
drug in the brain and reduce side effects by clearing the drug from
the blood quickly. Phenserine's rapid disappearance from the blood
suggests that it will represent a more tolerable treatment option to
existing therapies. At the same time, the drug binds potently but
reversibly to acetylcholinesterase in the brain allowing it to have a
longer duration of therapeutic action.
About
Alzheimer's Disease
Alzheimer's
Disease is a neurodegenerative disease that leads to progressive
dementia. A definitive diagnosis can be confirmed post-mortem by the
presence of amyloid plaques in the brain and neurofibrillary tangles
inside the neurons. It is a progressive disease characterized by loss
of function and death of nerve cells in several areas of the brain,
leading to loss of mental functions such as memory and learning.
Alzheimer's Disease is the most common cause of dementia, affecting
approximately 10-12% of Americans over the age of 65 with a total cost
of care of roughly $100 billion. It is the third most costly disease
in the U.S., following cancer and cardiovascular disease.
Audio News
Conference
SeniorJoural.com
readers can listen to an audio replay of a telephone news conference
on this announcement by dialing 1-800-428-6051 using this pass code -
236493 - through April 12.
To learn more
about Phenserine research by Axonyx -
Click Here
To learn more
about Alzheimer's Research by Axonyx -
Click Here
About Axonyx
Axonyx Inc. is a
US-based biopharmaceutical company engaged in the acquisition and
development of proprietary pharmaceutical compounds and new
technologies useful in the diagnosis and treatment of Alzheimer's
Disease and other cognitive disorders.
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