Drug
May Restore Memory With
Alzheimer's Disease
Tuesday November 13, 9:43
am ET
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also found on the Medical News TODAY website: http://www.medicalnewstoday.com/articles/88664.php
2006
study by MetLife found that adults over age 55 fear
Alzheimer’s disease more than cancer, and with
good reason. Alzheimer’s creeps up on patients
and their families, robbing more than half of all Americans
over age 85 of their memory and ability to care for
themselves. But what is perhaps most frightening is
that available treatments for the disease are by and
large ineffective.
Research from Georgetown University several
years ago suggested that a new class of anti-Alzheimer’s
molecule, spirostenols, might undo some of
the characteristic pathophysiology of Alzheimer-affected
brains. Further testing showed that one such
molecule, Caprospinol, actually reversed the
course of an Alzheimer-like condition induced
in rats. Today, Samaritan Pharmaceuticals
(Las Vegas, NV), is gearing up for human clinical
studies with this compound, also known as
SP-233.
Buildup of beta-amyloid plaque in the brain
has been recognized as a hallmark sign of
Alzheimer’s for close to a century.
Significant research points to this buildup
as a causative factor in the development and
progression of the disease. Until recently
this hypothesis could not be tested definitively
because of a lack of treatments that eliminate
beta-amyloid plaques.
Samaritan Pharmaceutical scientists, working
with leading researchers from Georgetown and
McGill Universities, have demonstrated in
a rat animal model, used to test new innovative
drugs for Alzheimer’s disease, that
Caprospinol clears amyloid plaque from the
brain and restored memory. More impressively,
treated rats perform as well or better in
standardized behavioral tests than healthy
control animals. In addition to eliminating
plaque, Caprospinol appears to reverse the
damage to memory and cognition that amyloid
plaque causes.
Dr. Vassilios Papadopoulos, of McGill University
Health Center, an adviser to Samaritan, and
the discoverer of anti-Alzheimer’s spirostenols
recently published a paper reviewing current
development-stage approaches to treating Alzheimer’s
disease (Recent Patents on CNS Drug Discovery,
2007, 2, 113-123). In this article, he identified
amyloid plaque as a key target for therapy.
The paper also summarized the research on
acetylcholinesterase inhibitors as well as
beta-amyloid aggregation inhibitors, of which
Caprospinol is an example.
The rat studies were conducted by treating
rats with a method of inducing an Alzheimer’s-like
condition in test animals within four weeks.
Rats treated in this fashion gradually lose
cognitive skills, as well exhibiting a host
of pathophysiologic brain changes indicative
of Alzheimer’s. Then treatment of sick
rats with Caprospinol brought about significant
positive changes in brain pathology. Neuritic
plaques, neurofibrillary tangles, astrogliosis,
microgliosis, neuronal death, and tissue shrinking
were all either reversed or markedly improved.
Why another Alzheimer’s drug?
One might ask why the world needs another
Alzheimer’s disease drug. The answer
lies in the relatively poor performance by
existing Alzheimer’s medications.
Of the five Alzheimer’s disease drugs
approved in the U.S., four (Razadyne®,
Exelon®, Aricept®, and Cognex®)
are inhibitors of cholinesterase, an enzyme
that shuts down the activity of the neurotransmitter
choline. Cholinesterase inhibitors are approved
for mild to moderate Alzheimer’s. The
fifth medication, Namenda®, is an antagonist
of the N-methyl D-aspartate receptor which
regulates glutamate, another neurotransmitter.
None of these agents cure Alzheimer’s
disease or significantly change the course
of the disease. The best that some patients
can expect is a delay in symptom progression
and/or improvements in some memory and behavioral
functions.
Enhancement of neurotransmitter activity is
a logical approach to treating AD. However,
there are problems with cholinesterase and
glutamate-acting agents. The first is that
they do not address the underlying pathology
of Alzheimer’s, treating only the symptoms
and not the disease. The second, related shortcoming
is that the most responsive patients get worse.
The positive benefits of drug treatment are,
disappointingly, measured in weeks or at best,
months. Alzheimer’s drugs also tend
to be quite expensive, and organ toxicities
are not uncommon.
Based on the chemical structure of cholesterol,
Caprospinol is an entirely new anti-Alzheimer’s
compound and works completely different than
the currently approved neurotransmitter agents.
Although the exact mechanism has not yet been
elucidated, molecular modeling experiments
suggest that Caprospinol inserts itself inside
the folded structure of the beta-amyloid peptide,
preventing amyloid molecules from joining
together into the highly neurotoxic amyloid-derived
diffusible ligands (ADDLs). It is this mechanism
that researchers believe causes amyloid plaque
wash out of the brain. Scientists also hypothesize
that through binding, Caprospinol prevents
ADDLs from entering neuronal mitochondria,
the energy-producing structures in all living
cells.
Samaritan has recently received the go-ahead
from the U.S. Food and Drug Administration
to test Caprospinol on a small group of patients
in a Phase I human safety trial. Thus far
results from animal toxicology tests are extremely
encouraging. No toxicity was observed in animal
studies. Although it is a steroid, the drug
does not appear to interfere with the body’s
steroid receptors or liver function either.
And since it does not affect with the cytochrome
P450 enzyme system, investigators believe
that SP-233 should cause no unanticipated
interactions with other medications that Alzheimer’s
patients are likely to be taking. Acting in
the liver, the P450 enzymes are responsible
for metabolizing and helping to eliminate
drugs and other chemicals.
The Phase I trial on Caprospinol is expected
to begin in Q2 2008.
For more information, log on to http://www.samaritanpharma.com.
|
Samaritan
Pharmaceutical scientists, working with leading
researchers from Georgetown and McGill Universities,
have demonstrated in a rat animal model, used
to test new innovative drugs for Alzheimer’s
disease, that Caprospinol clears amyloid plaque
from the brain and restored memory. More impressively,
treated rats perform as well or better in standardized
behavioral tests than healthy control animals.
In addition to eliminating plaque, Caprospinol
appears to reverse the damage to memory and cognition
that amyloid plaque causes. |
