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An
end to animal testing for drug discovery?
An
end to animal testing for drug discovery?
Date:
March 18,
2014
Source:
American Chemical Society
Summary:
As some countries and companies roll out new rules to
limit animal testing in pharmaceutical products designed for people, scientists
are stepping in with a new way to test therapeutic drug candidates and
determine drug safety and drug interactions -- without using animals. The
development of "chemosynthetic livers" could dramatically alter how
drugs are made.
...............................
As some
countries and companies roll out new rules to limit animal testing in
pharmaceutical products designed for people, scientists are stepping in with a
new way to test therapeutic drug candidates and determine drug safety and drug
interactions -- without using animals. The development of "chemosynthetic
livers" could dramatically alter how drugs are made.
This
research was presented at the 247th National Meeting &
Exposition of the American Chemical Society.
Mukund
Chorghade, Ph.D., noted that the European Union enacted new regulations in
2010, known as REACH, that aim to dramatically reduce the use of animals in
testing. But the development of new pharmaceuticals still depends heavily on
the time-consuming and expensive process of animal testing.
"Researchers
in drug discovery make small quantities of new potential drug compounds and
then test them in animals," said Chorghade, who is chief scientific
officer of Empiriko Corporation and president of THINQ Pharma. "It is a
very painstaking, laborious and costly process. Frequently, scientists have to
sacrifice many animals, and even after all that, the results are not
optimal."
Typically,
when researchers are onto a new compound that could address an unmet human
health need, they test it on animals to see if it's toxic before taking it into
clinical trials with human subjects. They figure this out by doing something
called metabolic profiling. That is, after giving an animal a test drug, the
experimental compound does its designated job in the body until the liver
breaks it down. Then researchers try to detect the resulting, minute amounts of
molecular byproducts, or metabolites. It's these metabolites that are often
responsible for causing nasty side effects that can derail an otherwise
promising therapeutic candidate.
This is
where Empiriko's patented chemosynthetic liver technology (Biomimiks™) comes
in. Chorghade has developed these stand-ins, which are catalysts that act
similarly to a group of enzymes known as cytochrome P450. Catalysts are
substances that speed up processes that otherwise wouldn't happen or would
occur slowly. Many of these cytochrome P450 enzymes break down drugs in the
liver.
So rather
than using lab animals, researchers could figure out metabolic profiles of
drugs by mixing them in test tubes with chemosynthetic livers. Chorghade's team
at Empiriko has already demonstrated how Biomimiks™ works with several
pharmaceutical compounds.
"These
chemosynthetic livers not only produce the same metabolites as live animals in
a fraction of the time," Chorghade said, "but they also provide a
more comprehensive metabolic profile, in far larger quantities for further
testing and analysis."
Other
possible applications are cropping up for these chemosynthetic livers. One of
Empiriko's scientific advisors suggested the use of Biomimiks™ to detoxify
blood for liver transplant patients. Biomimiks™ could also be used in the near
future to predict side effects when multiple drugs are taken together.
"The
average American above 60 years of age is taking multiple drugs a day,"
Chorghade explained. "Side effects from drug-to-drug interactions could be
substantial." In a case study, Chorghade and collaborators looked at two
drugs commonly taken together, one for high cholesterol and the other for type
2 diabetes. They found that the cholesterol drug sped up the breakdown of the
other one, which could potentially lower its effectiveness.
The
chemosynthetic livers aren't yet approved to take the place of animal tests.
But Chorghade is optimistic. His group has tested more than 50 drugs so far to
show that the catalysts accurately mimic how the human body processes them. He
said that they're working to get that number up to 100, which is what the U.S.
Food and Drug Administration requires for regulatory approval.
Chorghade
acknowledges funding from a private investor responsible for supporting this
technology to date.
Story
Source:
The above
story is based on materials provided by American Chemical Society. Note: Materials may be
edited for content and length.
