Gamma Secretase Modulators Show Promise in Alzheimer's Disease Animal Model Efficacy...

Gamma Secretase Modulators Show Promise in Alzheimer's Disease Animal Model
Efficacy Studies, According to Research Conducted by TorreyPines Therapeutics

LA JOLLA, Calif., March 31 /PRNewswire/ -- Gamma secretase modulators
(GSMs) have shown promise in Alzheimer's disease animal model efficacy
studies, according to research conducted by TorreyPines Therapeutics, Inc.
(Nasdaq: TPTX).
Presented by Steven Wagner, Ph.D., the company's Chief Scientific Officer,
at the recent Keystone Symposium on Alzheimer's Disease, data demonstrated
that GSMs provide a more selective mechanism than gamma secretase inhibitors
(GSIs). The in vivo research involved internally discovered and optimized
compounds that modulate the g-secretase complex without inhibiting its
catalytic activity. These GSMs appear to reduce the formation of the longer
pathogenic Ab peptides (e.g, Ab42) and allow the g-secretase enzyme complex to
generate the shorter, less fibrillogenic Ab peptides such as Ab38 and Ab37 and
to perform its other necessary functions.
"We have identified a series of GSM compounds that are intended to
modulate the enzyme's activity without preventing it from performing its
normal functions," said Dr. Wagner. "These orally bio-available, small
molecule GSMs appear to have addressed some of the pitfalls associated with
the GSI compounds, which have been associated with side effects. The
significance of our findings is that we may be able to selectively attenuate
the pathological functions of this enzyme complex without affecting the other
critical physiological functions it performs."
The major pathological hallmark of Alzheimer's disease is the abundance of
deposits called neuritic plaques in key areas of the brain that control memory
and cognition. These neuritic plaques are largely comprised of aggregations of
fibrillar peptides referred to as amyloid b, or Ab peptides. Evidence
indicates that individuals genetically predisposed to early-onset forms of
Alzheimer's disease make a greater proportion of the longer Ab peptides,
especially Ab42, relative to unaffected individuals. All of these Ab peptides,
including the pathogenic Ab42 peptide, are derived via proteolysis from a much
larger precursor molecule known as the amyloid b precursor protein (APP).
During normal catabolism, two crucial enzymes, or proteases, are
responsible for generating these Ab peptides from APP. The first enzyme, beta
secretase (b-secretase), cuts the APP molecule into two major pieces comprised
of a soluble extracellular fragment and a membrane-associated fragment. The
second enzyme, gamma secretase (g-secretase), then cleaves the membrane-
associated fragment into one of several different Ab peptides that vary in
length from 34 to 42 amino acids.
About TorreyPines Therapeutics
TorreyPines Therapeutics, Inc. is a biopharmaceutical company committed to
providing patients with better alternatives to existing therapies through the
research, development and commercialization of small molecule compounds. The
company's goal is to develop versatile product candidates each capable of
treating a number of acute and chronic diseases and disorders such as
migraine, chronic pain, muscle spasticity and rigidity, xerostomia and
cognitive disorders. The company is currently developing four product
candidates, two ionotropic glutamate receptor antagonists and two muscarinic
receptor agonists. Further information is available at
http://www.torreypinestherapeutics.com.
This press release contains forward-looking statements or predictions.
Such forward-looking statements include, but are not limited to, statements
regarding the potential for GSMs as a treatment for Alzheimer's disease. Such
statements are subject to numerous known and unknown risks, uncertainties and
other factors, which may cause TorreyPines' actual results to be materially
different from historical results or from any results expressed or implied by
such forward-looking statements, including whether any preclinical studies or
clinical trials conducted in the future, will prove successful, and if
successful, whether the results can be replicated; or whether safety and
efficacy profiles the GSMs will be established, or if established, will remain
the same, be better or worse in future clinical trials, if anyThese and other
risks which may cause results to differ are described in greater detail in the
"Risk Factors" section of TorreyPines' annual report on Form 10-K for the year
ended December 31, 2006 and TorreyPines other SEC reports. The forward-looking
statements are based on current information that is likely to change and speak
only as of the date hereof.
Company Contact:
Ev Graham
TorreyPines Therapeutics, Inc.
858-623-5665, x118
egraham@torreypinestherapeutics.com

Media Contact:
David Schull
Russo Partners, LLC
212-845-4271
david.schull@russopartnersllc.com

Investor Contact:
Rhonda Chiger
Rx Communications
917-322-2569
rchiger@rxir.com

Investor Contact:
John Baldissera
BPC Financial Marketing
800-368-1217

SOURCE TorreyPines Therapeutics, Inc.

Company Contact, Ev Graham of TorreyPines Therapeutics, Inc., +1-858-623-5665,
ext. 118, egraham@torreypinestherapeutics.com; Media Contact, David Schull of
Russo Partners, LLC, +1-212-845-4271, david.schull@russopartnersllc.com;
Investor Contact, Rhonda Chiger of Rx Communications, +1-917-322-2569,
rchiger@rxir.com, or John Baldissera of BPC Financial Marketing,
+1-800-368-1217