Synvista Therapeutics,
Inc. (Amex: SYI) announced results of a series of preclinical studies
designed to explain the mechanism underlying dysfunctional high density
lipoprotein (HDL), that creates a defect in reverse cholesterol transport
in patients with Diabetes Mellitus (DM). The studies reveal that a common
blood protein, Haptoglobin, binds to the core of HDL and that a defective
Haptoglobin variant (Hp2-2), found in 40% of the population, may induce
dysfunctionality in HDL. Further, the studies report that exposure to
Vitamin E can restore HDL functionality and the process of reverse
cholesterol transport. The study is being presented today at the American
Heart Association's (AHA) Scientific Sessions 2007 in Orlando, Florida.
"We are very pleased with the outcome of these studies, as we believe
they provide scientific rationale for our current development platform,
including our work developing a diagnostic test for Haptoglobin type, to
determine cardiovascular risk and a therapeutic product to decrease HDL
oxidation and restore reverse cholesterol transport function," said Noah
Berkowitz, M.D., Ph.D., President and Chief Executive Officer of Synvista.
"This study further demonstrates that the Hp2-2 phenotype, a risk factor
for cardiovascular events in patients with diabetes, may function by
interfering with the function of HDL and promoting inflammatory
atherosclerosis."
The experiments of Rabea Asleh, M.D., of the Rappaport Faculty of
Medicine and Research Institute, at the Technion, Haifa, Israel, who is
today's recipient of the AHA's Council on Nutrition, Physical Activity and
Metabolism's 2007 New Investigator Award, provided a mechanistic
explanation for the defect in reverse cholesterol transport observed in
many patients with diabetes mellitus (DM). Reverse cholesterol transport
describes the process of moving cholesterol out of the atherosclerotic
plaque and into HDL particles ("good cholesterol"). This process is thought
to be the mechanism by which high levels of HDL protect patients from
atherosclerotic disease. Dr. Asleh reports the presence of
Haptoglobin-Hemoglobin (Hp-Hb) complexes in HDL particles and observes that
Hp2-2-Hb complexes promote less efficient reverse cholesterol transport in
DM, which can be reversed by antioxidants such as vitamin E. He proposes
that strategies targeted to decrease oxidation of HDL in Hp2-2 patients may
improve HDL function. Synvista has completed enrolling two cohorts of a
three cohort Phase 2 clinical trial, evaluating among other endpoints, the
impact of the Company's oxidized lipid metabolizing agent, ALT- 2074, on
functional reverse cholesterol transport.
Radiolabeled Hp2-2-Hb complexes injected into mice and rats with and
without diabetes demonstrated significantly longer half-life then
radiolabeled Hp1-1-Hb complexes (e.g. 2-3 fold longer in non-DM animals,
p=0001; and doubled in DM mice, p= 0.005). Coimmunoprecipitation studies
showed that there is 10-fold more Hp2-2-Hb complex associated with HDL in
diabetic mice than Hp1-1-Hb in non-DM mice. This was also shown in human
sera where significantly more radioactive hemoglobin is associated with HDL
particles in Hp2-2 individuals than Hp1-1 individuals. Reverse cholesterol
transport, as measured by radiolabeled cholesterol efflux from pre-loaded
macrophages, was significantly impaired (p=0.0001) by incubation with serum
from Hp2-2 diabetic mice versus serum from non-DM Hp2-2 mice. This
impairment was restored to normal levels when the mice received vitamin E.
About Synvista Therapeutics
Synvista Therapeutics is a biopharmaceutical company developing small
molecule drugs to treat and prevent cardiovascular disease and to treat
nephropathy in people with diabetes. The Company has identified several
product candidates that it believes represent novel approaches to some of
the largest pharmaceutical markets. The Company's portfolio includes orally
bioavailable, organoselenium mimics of glutathione peroxidase. These
compounds metabolize lipid peroxides and have the potential to limit
myocardial damage subsequent to a myocardial infarction. The Company is
developing a clinical diagnostic test, based on cardiovascular risk
assessment, using Haptoglobin characterization, to identify patients at
high risk for cardiovascular complications of diabetes.
Synvista Therapeutics also is developing alagebrium, a proposed breaker
of AGEs for the treatment of diastolic heart failure. This disease
represents a rapidly growing market of unmet medical need, particularly
common among diabetic patients. Alagebrium has demonstrated relevant
clinical activity in two Phase 2 clinical trials in heart failure, as well
as in animal models of heart failure and nephropathy, among others.
Alagebrium has been tested in approximately 1,000 patients in multiple
Phase 1 and Phase 2 clinical trials, allowing Synvista Therapeutics to
assemble a sizeable human safety database. For more information, please
visit the Company's website at synvista.
Any statements contained in this press release that relate to future
plans, events or performance are forward-looking statements that involve
risks and uncertainties including, but not limited to, the risks associated
with the events described in this press release, future clinical
development of Synvista Therapeutics' product candidates, and other risks
identified in Synvista Therapeutics' filings with the Securities and
Exchange Commission. Further information on risks faced by Synvista are
detailed under the caption "Risk Factors" in Synvista Therapeutics' Annual
Report on Form 10-K for the year ended December 31, 2006. These filings are
available on a website maintained by the Securities and Exchange Commission
at sec. The information contained in this press release is
accurate as of the date indicated. Actual results, events or performance
may differ materially. Synvista Therapeutics undertakes no obligation to
publicly release the result of any revision to these forward- looking
statements that may be made to reflect events or circumstances after the
date hereof or to reflect the occurrence of unanticipated events.
Synvista Therapeutics, Inc.
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