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CNO TECHNOLOGY
SynZyme's
target-specific caged nitric oxide (CNO) therapeutics are based on
biologic or non-biologic compounds that have a simple, catalytic,
enzyme mimetic action. These compounds can scavenge or dismutate
reactive oxygen or nitrogen species (ROS/RNS), which are
overproduced in various kinds of disorders or diseases, specifically
at the site where the injuries occur. ROS/RNS are highly reactive
and can injure cell membranes, trigger cell processes that lead to
tissue inflammation, and damage DNA as well as cause vascular damage
and vasoconstriction. In some circumstances, this damage can have
severe or even lethal consequences.
Nitric oxide
(NO) is produced in the body, and the identification of the
molecule's key role in biological signaling. In 1998, in recognition
of the medical significance of the molecule, the Nobel Prize in
Physiology was awarded to the scientists who discovered the role of
NO as a biological messenger.
NO in its
"caged" form, (i.e. CNO) is a stable free radical also known as
nitroxide or spin label. The two forms of NO are different
functionally. For example, while nitric oxide reacts with elevated
levels of ROS to form toxic radicals termed peroxynitrite, CNO
catalytically breaks down peroxynitrite. It is, in addition, a much
more stable molecule than nitric oxide.
CNO by itself is
not an ideal therapeutic agent. CNO is a small molecule and
therefore is susceptible to being rapidly removed by normal bodily
processes. This limits CNO's ability to remove excess reactive
molecules, since the molecule is only around for a short time before
it is cleared by the body. In addition, CNO tends to distribute
evenly throughout all body tissues and fluids. This also limits its
therapeutic efficiency because a great deal of the agent must be
applied to reach an effective concentration in any target tissue.
SynZyme's technology circumvents these problems by binding the CNO
to target-specific carrier molecules. Binding CNO to carrier
molecules confers many advantages. If a carrier is selected that is
too large to escape from blood vessels, for example, then the
catalytic action will be confined within the blood vessel. If, on
the other hand, the CNO is bound to a small, fat-soluble molecule,
then the catalytic action can be localized to cell membranes. As an
additional benefit, it is possible to select carrier molecules that
have additional therapeutic actions of their own.
The clinical
indications that can be addressed by the CNO and target-specific
carrier molecules are limited only by our ability to design these
molecular complexes. For instance, one of SynZyme's products uses a
CNO and hemoglobin carrier, i.e. HemoZyme. This complex remains in
blood vessels, delivers oxygen to tissues, and catalytically removes
reactive oxygen and nitrogen species. A second SynZyme product is
composed of CNO combined with a small, fat-soluble molecule, i.e.
DermoZyme, that is constructed so that skin cellular enzymes will
attack it. This complex penetrates into cells, is "clipped" by the
cellular enzymes, lose it's fat-soluble characteristic, and ends up
trapped in the cell - thereby localizing the CNO's catalytic
activity inside the cell. In the above examples, HemoZyme is
designed to treat blood loss, while DermoZyme can be applied
topically to the skin to prevent radiation-induced damage such as
sunburn or hair loss during cancer radiation therapy.
Moreover, two or
more different caged nitric oxide and carrier constructs can be
combined to further enhance therapeutic action. For instance, one of
SynZyme's therapeutic regimens uses CNO bound to albumin, i.e. VACNO,
which is compartmentalized within blood vessels for the treatment of
acute stroke and vaso-occlusive crisis in sickle cell disease.
VACNO along with second CNO compound that can "shuttle" back and
forth between cells in tissue and the blood vessels. This allows the
albumin-based CNO molecules to "recharge" the second type of CNO
molecules - yielding a sustained therapeutic effect in the tissue.
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