FOR IMMEDIATE RELEASE
September 10, 2009
Contact: Donna Krupa
Office: (301) 634-7209
dkrupa@the-aps.org
Leading Expert Examines
Status, Promise Of Key Human Protein – Endothelin –
At Conference Hosted By American Physiological Society (APS)
 MONTREAL, CN (September 10, 2009) − One of the
most intriguing developments in recent medical science is the discovery of
the human chemical endothelin (ET). Since its detection in 1988, over 22,000
scholarly articles (about 3 per day) have been published on the subject, a
new class of drugs has been developed, and 25 Phase I, II and III clinical
trails are now underway. As the scientific and medical communities involved
in ET move towards 25 years of understanding the protein, which future
developments hold potential? At what risk? Do medicinal compounds look
promising?
Donald Kohan, Professor of Medicine in the Division of
Nephrology at the University of Utah Sciences Center and a leading global
expert on endothelins is addressing these and other issues at the 11th
International Conference on Endothelin being held September 9-12, 2009
in Montreal, CN. Dr. Kohan’s invited presentation, “Clinical Relevance of ET
Antagonist: An Update,” is part of the program being sponsored by the
American Physiological Society (APS;
www.the-aps.org). A copy of the complete program is at
http://the-aps.org/meetings/aps/ET11Montreal/index.htm.
What is Endothelin?
Identified in 1988, ET is produced by most tissues in
the body. The protein is highly concentrated in the brain, lungs, kidney,
heart, blood vessels and even in some cancer cells. ET is also the most
potent vasoconstrictor (causing the blood vessels to constrict) known. It
plays a major role in embryonic development and disease.
ET binds to two different types of receptors:
endothelin A (ETR-A) and endothelin B (ETR-B). When ET
connects with its receptors they react in different ways and have different
impacts on disease.
The activated ETR-A
receptor sends a signal to the blood vessels to contract, which then
increases blood pressure. Conversely, when the ETR-B receptor is
activated it signals the blood vessels to expand, thereby leading to a
decrease in blood pressure.
ET can play a role in health and disease. In health, ET
can regulate blood pressure and assist in normal cell growth. However,
excessive ET production can lead to kidney, blood vessel, lung and heart
disease. In addition, because ET can act as a growth factor through
activation of ETR-A, ETR-A blockade may inhibit tumor
growth or prevent cancer from metastasizing
A New Class of Drugs: Endothelin Blockers
In an attempt to reduce the deleterious effects of ET,
scientists have recently developed a new class of drugs. The drugs, known as
ET receptor antagonists, bind to the ET receptors and block ET actions.
Since the U.S. Food and Drug Administration (FDA) approved the first ET
receptor antagonist drug in 2001 (for pulmonary hypertension), two
additional related compounds have been approved.. These drugs
block either ETR-A alone or both ETR-A
and ETR-B receptors. Most recently, the FDA approved a combined
ET receptor blocker for the treatment of scleroderma, a disease complicated
by ulcers on fingers and toes.
“Endothelin Antagonists Present Great Promise”
“Endothelin antagonists present great promise,”
according to Dr. Kohan. To support his view, Kohan points out that studies
being conducted in animals and humans suggest that there is a role for
targeting ET receptors in kidney disease, difficult to treat high blood
pressure, pulmonary hypertension and other disorders. In addition, studies
in animals suggest that ET blockers may be of benefit in traumatic brain
injury, eye disease and other conditions.
At the same time there are challenges. One challenge is
how best to determine which diseases should be treated by targeting A
receptors or the A and B receptors combined. Researchers do not currently
have a full understanding of how ET receptors always interact with one
another. Another consideration is drug side effects. “Studies need to be
conducted on ET receptor antagonist-associated toxicity, especially as it
relates to possible testicular toxicity, hepatic dysfunction and fluid
retention,” Kohan says. He also noted that ET receptor blockers should never
be taken by pregnant women since ET aids fetal development.
Despite the challenges Kohan believes therapy with ET
receptor antagonists hold great promise. After 21 years of examining the
protein, Kohan says many scientists and physicians believe that ET is a rich
target for the development of new receptor antagonist drugs. Says Kohan,
“The antagonists are now clinically approved to treat a few diseases and we
look forward to their being of substantial benefit in many more diseases.”
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Physiology is the study of how molecules, cells, tissues and organs
function to create health or disease. The American Physiological Society (APS;
www.the-APS.org/press) has been an integral part of the discovery
process since it was established in 1887.
To view the
complete program for the International Conference on Endothelin
conference, log on to
http://the-aps.org/meetings/aps/ET11Montreal/index.htm.
To schedule an interview with Dr. Kohan please
contact Donna Krupa, 301.634.7209,
DKrupa@the-APS.org
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