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Wonder Drugs Using Pharmazooticals

New drug discovery from unusual animal sources is just around the
corner.

By Leanna Skarnulis WebMD Feature Reviewed By Brunilda Nazario, MD
Monday, December 08, 2003

Unless you're a scientist, you might not find much to love about pigs'
and cows' pancreas, horse urine, snake and spider venom, or Gila
monster spit. Yet all of these are existing or potential sources of
drugs, some of which are life-saving. These "pharmazooticals"
represent just a small portion of drugs derived from natural sources.
In western medicine -- plants rule.

Modern investigation of animal sources may have started in 1921, back
when they called diabetes "sugar disease." The Nobel prize-winning
work of Canadian surgeon Frederick Banting and his assistant Charles
Best led to the discovery of insulin and its ability to lower blood
sugar. It's estimated that since that time, insulin -- mainly derived
from the pancreas of pigs and cows -- has saved the lives of 15
million people with diabetes.

Today, another creature brings hope to people with type 2 diabetes
whose blood sugar levels remain high in spite of treatment. An
investigational drug called exanetide comes from lizard spit,
specifically an enzyme in the venom of the Gila monster. It also
appears to promote weight loss.

We have the animal kingdom to thank for some very important drugs
already in use. The ACE inhibitor Captopril used to lower blood
pressure comes from the Brazilian arrowhead viper. ARA-C, modeled
after compounds from the Caribbean sponge, treats leukemia and
lymphoma. Integrelin, which comes from a protein in the venom of the
southeastern pygmy rattlesnake, is used to treat acute coronary
syndrome. Calcimar and Miacalcin are calcitonin hormones derived from
Coho salmon and used to treat osteoporosis.

One of the most widely used and most controversial drugs derived from
animals is Premarin, an estrogen given as menopausal hormone therapy.
The drug is derived from the urine of pregnant horses, and the
treatment of those animals and their foals on so-called PMU (pregnant
mares' urine) farms have come under attack from animal rights groups.

Animal rights issues may be one reason most scientists look mainly at
spiders, reptiles, and sea creatures rather than at mammals, says
Elliott Sogol, PhD, spokesman for the American Pharmacists
Association. "I think there's always been hesitation from researchers
because of organizations that don't want to see any animals used for
research, and maybe some concern about coming from an ethical
standpoint. If you're just milking a snake you're not harming it."
Another reason might be that reptiles and spiders are more readily
available and easier to handle, says Sogol, who is pharmaceutical
sciences director at Campbell University in Buie, N.C.

Mother Nature Knows Best

Some scientists once predicted that doing drug discovery in nature
would be made obsolete by laboratory synthesis of various molecules
and computer simulations, a field known as combinatorial chemistry.
But Mother Nature has a dazzling array of sophisticated, natural
products.

It's hard to exaggerate the potential for drug discovery in nature's
storehouse. Jerrold Meinwald, PhD, researches the role of chemistry in
insect interactions, especially how they employ chemicals in mating,
defense, and communication. Some of these chemicals, such as
components of spider venom, may prove to have medical applications.
"The venom they inject to paralyze prey contains novel neurotoxins
that block certain receptors," he says. "It would seem very promising
to go after spiders that haven't been looked at as potential
neuropharmacological agents."

That would be a lot of spiders. Meinwald tells WebMD perhaps only 100
to 200 of the 30,000 known spider species have been studied. "There
are many lifetimes of work," says Meinwald, who is Goldwin Smith
Professor at Cornell University in Ithaca, N.Y.

One company, NPS Pharmaceuticals, specializes in researching and
developing drugs based on spider and scorpion venoms. In the pipeline
is a new class of drugs called "delucemines" (NPS1506) which act to
protect brain cells and minimize brain cell death in stroke victims
until blood flow can be restored. The drugs might also have potential
in the treatment of depression.

With spiders, as with most species, the goal is to synthesize the
active chemicals rather than depend on animals. "You can milk spiders'
venom without killing them, but you don't get sufficient quantities,"
says Meinwald.

Synthesizing drugs to preserve the properties of a natural drug can be
challenging. For example, Sogol tells WebMD some ingredients from
saliva stay longer in the human body than a synthetic version.
"They'll stay in the body longer, and that can be very positive. If
you have diabetes and your current drug lasts four hours, it's better
to have one that lasts 12 hours." From One Beautiful, Deadly Snail

The cone snail is celebrated for its beauty and feared for its poison,
which on occasion has been known to kill swimmers. The deadly venom,
however, is exceptionally rich in compounds called conopeptides that
could be used or synthesized to make an array of pharmaceuticals.
Cognetix, Inc., is researching applications for acute and chronic
pain, epilepsy, local anesthesia, heart disease, stroke, neuromuscular
back pain, multiple sclerosis, and spinal cord injury. Scientists are
urging protection of the cone snail, which is on the brink of
extinction.

On the Horizon

Here are some of the areas in which drugs derived from animals are
being investigated:

* Painkillers. ABT 594 comes from the skin of the South American frog.
It appears to be more effective than morphine without being addictive.
* Cancer. TM 601 is derived from the Israeli yellow scorpion and
attacks malignant brain tumors called glioma tumors responsible for
two-thirds of the cases of brain cancer, without harming healthy
cells. ET 743, which comes from sea squirts, is being tested for
treatment of ovarian cancer and soft tissue sarcoma.
* Stroke. Ancrod, which will be marketed in the U.S. as Viprinex
pending FDA approval, is an anticoagulant with potential to prevent
cell damage and death when someone suffers a stroke. The active
ingredient comes from the venom of the Malaysian pit viper. In
Germany, where Ancrod has been marketed for a number of years, a
specially built facility houses about 3,000 snakes. Several other
sources of anticoagulants are being looked at. "We're still trying to
find medicine that will be useful long-term for stroke victims," says
Sogol. "There's saliva of vampire bats, for example. When they bite
their prey, the enzyme in their saliva doesn't allow blood to clot.
There's also something in the saliva of leeches that is an
anticoagulant."
* Antibiotics. A substance called magainin 2 -- comes from the skin of
frogs and looks promising in the search for antibiotics that bacteria
can't develop resistance to. Studies began when biomedical researcher
Michael Zasloff, MD, PhD, of Georgetown University in Washington,
D.C., wondered how frogs could swim in filthy ponds without getting
sick.

Save the Rainforest

One of the most biodiverse and pharmaceutically promising regions of
the world is the Brazilian rainforest, yet it's rapidly disappearing
-- along with untold numbers of plant and animal species -- because of
clearcutting. Moreover, fewer and fewer nations are now willing to
collaborate with foreign researchers. "It's become very hard to
establish any sort of international research effort because someone
will say that the amount of financial reward offered to the supplier
of natural products isn't fair," says Meinwald. "It's the concept of
'bio-piracy.' They think drug companies take their valuable resources,
make a fortune and just give them crumbs. It's true that some drugs
can sell at the level of a billion dollars a year. What people don't
appreciate is that this happens, however, only after 10 or 12 years of
research and investment. Most drug candidates fall through because of
side effects or other problems."

How Did It all Begin?

When you think about folk remedies dating back before the dawn of
scientific discovery, what ever gave people the idea that, say, taking
cod liver oil would relieve a cold or eating pearls would cure
insanity?

"I don't know, but the same thing occurs to me about food," says
Meinwald. "How in the world would people decide you could eat oysters?
He surmises that people observed seagulls picking up oysters, dropping
them from high in the air to break them open, then swooping down to
eat them. Humans seem to have tried practically everything for eating.
They may have noticed by similar experimentation that some things make
you very sleepy or take away pain."

Published Dec. 8, 2003

http://my.webmd.com/content/article/78/95687.htm