http://www.smallcapcenter.com/news.asp?mysection=headlines&storyid=5429801

Drug Compound Restores Youth to Aging Arterial Cells in Elderly
Hypertensives, Hopkins Study Shows; Stiff Arteries Relax Like Younger
Blood Vessels After Taking Alagebrium

Nov 12, 2005 12:01:00 AM

The information in this press release is EMBARGOED until 10 a.m. EST
Tuesday, Nov. 15. AScribe Newswire is providing the release in advance
as a courtesy to the media.

ATTENTION: Medical editors

BALTIMORE, Nov. 15 (AScribe Newswire) -- A compound called alagebrium,
which is very similar to another used in anti-wrinkle creams, may be
useful in reducing the deleterious effects of arterial aging in the
majority of elderly Americans with systolic hypertension, a new study
from researchers at Johns Hopkins shows.

Systolic hypertension refers to higher than normal levels of the
"upper" number in a blood pressure reading, or with a lower than
normal "bottom" number, in this case a pressure of 140 millimeters of
mercury or greater and/or a diastolic pressure of less than 90
millimeters of mercury. Hypertension of this sort indicates stiffening
of the body's arteries.

"This is the first demonstration that this class of drugs, known as
collagen-crosslink breakers, can turn back the clock and make old
arteries behave like young ones," says senior study investigator and
geriatric cardiologist Susan Zieman, M.D., an assistant professor at
The Johns Hopkins University School of Medicine and its Heart
Institute. "There are many medications for routine hypertension, and
coronary artery disease or atherosclerosis, which can lead to heart
attack and heart failure, but none that help counteract the aging of
cells inside the arterial walls that often precedes symptoms of disease."

According to the American Heart Association, more than 65 million
Americans have high blood pressure, most of it of the systolic kind.
In systolic hypertension, the pressure or force of blood flow through
the arteries is too strong as blood is pumped by the heart's
ventricles (systole) to the rest of the body. Diastolic pressure, on
the other hand, is a measure of the pressure against arterial walls
when the heart is resting and refilling between beats.

The Hopkins researchers found that alagebrium, formally known as
ALT-711 or 4,5-dimethyl-3-(2-oxo-2-phenylethyl)-thiazolium chloride,
reduced stiffening in the vessel wall in the main artery of the neck
(carotid artery) by as much as 37 percent. The drug also improved
endothelial function, the ability of the vessels' inner lining to
relax and dilate in response to increased stress from blood flow, by
102 percent.

Chemically, alagebrium is a so-called crosslink breaker, responsible
for destroying the rigid chemical bonds known as advanced glycation
endproducts, or AGE for short, that form between body proteins and
sugars over time. According to Zieman, both stiffening and reduced
capacity of the arteries to expand in response to stress are common
effects of aging that occur when the crosslinks form in the body's key
structural proteins, such as collagen, or when AGEs interact directly
with enzymes that regulate blood flow.

Crosslinking effectively carmelizes the collagen - found in all parts
of the body, especially in the skin, eyes, blood vessels and nerves -
leading to tissue "wrinkles," cataracts, as well as stiffening and
increased speed and force of blood flow. These processes are
accelerated in diabetics whose blood sugar content is often elevated.

As hypertension becomes chronic, aging blood vessels lose their
ability to stretch and relax between heartbeats. The anti-wrinkle
effects of a crosslink-breaker treatment occur on facial skin because
the compound similarly lets collagen there relax, giving the skin a
plumper, smoother look.

The Hopkins findings, to be presented at the American Heart
Association's Scientific Sessions 2005 on Nov. 15 in Dallas, Texas,
also suggest that the cellular effects of aging caused by AGE are
potent targets for new therapies.

In the Hopkins study, 13 elderly men and women with systolic
hypertension took either daily doses of alagebrium (210 milligrams)
for eight weeks or a look-alike pill (placebo), containing no active
drug. AGE and collagen levels were monitored through blood tests.
Stiffness was measured using a small pressure-sensor device called a
tonometer.

Ultrasound readings, taken before and after drug therapy, were made as
a blood pressure cuff was inflated for five minutes and deflated. This
allowed researchers to calculate endothelial function based on how
much the blood vessel lining relaxed as a percentage increase of how
much the blood vessel could expand.

After treatment with alagebrium, neck arteries became less stiff, as
shown by tonometer readings and decreased levels of collagen in the
blood as AGE crosslinks were broken down. Analysis of additional
pressure-wave readings also showed flatter patterns more closely
resembling younger arteries than older, stiffer ones, which have wave
patterns with higher peaks.

While the results did not explain why endothelial function improved,
the researchers believe it has to do with the drug's effects on AGE
and cell function. Their theory, Zieman says, is that one chemical
reaction, the breakdown of AGE crosslinks, both reduces the structural
causes of arterial stiffness in the artery wall and alleviates the
detrimental effects of AGE on other enzymes or related proteins,
possibly nitric oxide and other chemicals causing vessel inflammation,
which are essential to regulating heart and blood vessel function.

"These results confirm that this drug does have important effects on
the aging process in the arteries, but we still have to prove that
there's some benefit to patients in terms of reducing cardiovascular
disease," Zieman says. "Our next step will be a study, expected to
begin in late 2006, of the drug's potential benefit at preventing or
reversing heart failure in the elderly."

Alagebrium has been under investigational study since 1999, originally
as a treatment for hypertension. While clinical studies have
demonstrated the drug's ability to loosen up stiff arteries, two
larger studies in older people with hypertension have not shown
significant results in lowering blood pressure.

Funding for this study, which took one year to complete, was provided
by the National Heart, Lung, and Blood Institute, a member of the
National Institutes of Health. Medication was supplied free of charge
by the drug's manufacturer, Alteon Inc., of Parsippany, N.J.

Improved Flow-Mediated Arterial Vasodilation by Advanced Glycation
Crosslink Breaker, Alagebrium Chloride (Alt-711), in Older Adults with
Isolated Systolic Hypertension. Vojtech Melenovsky M.D., Ph.D.; Lia
Clattenburg, B.A.; Mary Corretti, M.D.; Patricia Fitzgerald, R.N.,
B.S.N.; Anne Capriotti; Gary Gerstenblith, M.D.; David Kass, M.D., and
Susan Zieman, M.D., Ph.D.

- - - -

CONTACT: David March or John Sales, Johns Hopkins Medicine Office of
Corporate Communications, 410-955-1534, dmarch1(at)jhmi.edu

Media Contact: David March or John Sales, 410-955-1534,
dmarch1(at)jhmi.edu

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-----------------------------

Scott La Pidus

[Thanks for posting this. Essentially the same story was also posted to
sci.life-extension today. It comes as a much needed shot in the arm for Alteon,
which had been really suffering financially from setbacks on research relating
to this lead product. As a result their stock rose from 18 cents to just over
25. It is also interesting that one of the human trials used a dosage of 420 mg
daily to achieve good results. For details about this see the sle posting:
http://groups.google.com/group/sci.life-extension/browse_frm/thread/3c7cf5c82276\
0934

In addition, someone else who has tried higher dosages recently told me about
some good effects that he had which might be related. Therefore, upon restarting
taking ALT-711 (after a break to see if it was having any effect on my liver
enzymes) I have decided to double the dosage for me and Kitty to 3 mg/Kg.
--Paul]