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Forbes
June 16, 2008
Medical Technology: Fixing Pharma
Stem cells could lead to better, safer drugs
By Robert Langreth and Matthew Herper
Drug discovery is a cruel business. A hundred thousand people die every
year because of adverse drug side effects. Millions die too young
because drugs just aren't good enough.
The problem is that scientists invent medicines to treat people, but
they have to use animal or tumor cells to do it. Heart cells, brain
cells and liver cells all die when you try to keep them in a petri dish.
So over decades researchers have come up with jury-rigged tests. They
use preserved kidney cells extracted from a human fetus 30 years ago to
see if an experimental drug will disrupt the rhythm of the heart. They
use cells from a rat's digestive tract with human receptors stuck in.
They force huge doses of every potential medicine down the throats of
rodents. "The system is failing," says Gabriela Cezar, who left Pfizer
to study stem cells at the University of Wisconsin-Madison.
It's a testament to the ingenuity of pharmaceutical researchers that the
system works at all. Nine out of ten drugs studied in humans turn out
not to work or to be too toxic. Sanofi-Aventis, Pfizer and AstraZeneca
have all had promising compounds go up in flames because of dangerous
side effects. One solution may be to use embryonic stem cells to test
drugs for safety and efficacy. "You should be able to get rid of some of
the nasty drugs before they even hit clinical trials," says UW-Madison
stem cell pioneer James Thomson. "And we're able to do that today."
Two years ago Thomson founded Cellular Dynamics International, a biotech
firm that uses embryonic stem cells to make beating human heart cells,
something that's never before been available to drug companies. Thomson
has avoided the business world as long as possible but now says it is
time for his cells to go commercial. Roche is the first announced
customer. Earlier this year it began tests with Thomson's heart cells to
catch cancer drugs that are toxic to the heart. A rival company,
Sweden's Cellartis, is developing ways to test drugs for liver toxicity
(with AstraZeneca) and for birth defects (Pfizer).
Even bigger, but further off, is the potential that being able to study
neurons in a dish will allow researchers to understand what causes
Parkinson's or Lou Gehrig's disease. It could be that in 20 years almost
every medical researcher is going to use embryonic stem cells as basic
tools. "That is going to profoundly change medicine," says Thomson.
Catapulting this work forward is the discovery of ways to create cells
that act like embryonic stem cells but without ever using embryos. Last
year Japan's Shinya Yamanaka and Thomson simultaneously showed that
adult human cells could be transformed into embryolike stem cells by
activating only four genes using viruses. "That has galvanized the
field," says Alexander Rod MacKenzie, head of basic research at Pfizer.
UC-San Diego researcher Lawrence Goldstein is using these so-called
induced pluripotent stem cells to make neurons that are "genetically
identical" to those of Alzheimer's patients. He is collecting 50 skin
samples from Alzheimer's patients in order to hunt for new drugs.
Wisconsin's Cezar has started a biotech called Stemina that is using
stem cells to get to the roots of autism. Autism appears in a tenth of
the children born to mothers who take the epilepsy drug valproate.
Valproate is known to injure neurons, so Cezar is converting embryonic
stem cells into live neurons and adding valproate to the sample. The
neurons gush chemicals that she is comparing to those found in brain
cells of people with autism. If there's a match, Cezar could be on a
path toward diagnostic tests or drugs. Stemina is using a similar
strategy for a range of potential drugs. "[Autism] is an epidemic," she
says, "and we have no idea about the cause."
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