Parkinson's Treatment Tried in Rats Reduced Symptoms but Caused TumorsBy Rick Weiss
Washington Post Staff Writer
Nerve
cells grown from human embryonic stem cells and injected into the
brains of rats with a syndrome mimicking Parkinson's disease
significantly reduced the animals' symptoms, but the treatment also
caused tumors in the rodents' brains, scientists reported yesterday.
Researchers
said the work showed both the potential benefits and risks of human
embryonic stem cells, which have been highly touted for their capacity
to replace diseased tissue but are controversial because they are
derived through the destruction of human embryos.
"The behavioral
data validate the utility of the approach. But it also raises a
cautionary flag and says we are not ready for prime time yet," said
lead researcher Steven A. Goldman, a professor of neurology and
neurosurgery at the University of Rochester Medical Center.
Goldman
said he suspected that with modest changes in technique, researchers
will be able to keep the benefits of the treatment while eliminating or
reducing the chances of getting the cancerlike growths. But he conceded
that much more basic research would have to be done before scientists
-- or regulators -- were likely to be convinced of the approach's
safety.
In the experiments, Goldman and colleagues from the Weill
Medical College of Cornell University in New York treated
laboratory-cultured human embryonic stem cells in a new way that coaxed
many to become a kind of Neuron that produces dopamine, a
Neurotransmitter. Those cells are gradually lost in Parkinson's
disease, depriving the body of that essential chemical messenger.
The disease causes Motor problems such as trembling and muscle rigidity and a gradual decline in mental functioning.
The
team injected the cells into the brains of rats, which had been given a
chemical that causes damage similar to that seen in Parkinson's. The
new cells integrated into the animals' brains and produced copious
amounts of dopamine. As a result, the animals' motor coordination
improved almost to the point of being normal, according to the report
in yesterday's online edition of the journal Nature Medicine.
But
when the animals were autopsied after three months and their brains
were examined microscopically, the team found multiple tumors,
indicating that some of the injected cells did not settle into the job
of being neurons but rather had begun to grow uncontrollably.
The
results were similar to those of other experiments published Oct. 12 in
the online journal Stem Cells by a team led by Ole Isacson, a Harvard
Medical School professor of neuroscience and neurology. In that case,
the stem cells were cultivated differently, produced less dopamine and
had fewer beneficial effects. But some grew out of control.
"I
think it is a terrific demonstration that we are midway between
earliest discovery and clinical application," Isacson said Friday.
Goldman
and Isacson said they are developing technologies for culling from a
developing stem cell population those cells that are not fully
committing themselves to becoming neurons -- or selecting such fully
committed cells from a larger, mixed population.
"We still have
so little experience with these cells, but if we keep doing the work
and we do it carefully, then I believe that in the long run it will
help patients," Isacson said.
Thomas Okarma, president of Geron,
a California company that hopes to gain Food and Drug Administration
permission to treat spinal-cord-injury patients with modified embryonic
stem cells next year, said his company's cells have shown no sign of
causing tumor growth in any of its animal studies.
But he said the FDA has asked for additional extensive data on exactly that question before it will give its final okay.
"What
they worry about, and rightly so, is there are rogue undifferentiated
cells lurking in the cell population that we haven't detected," Okarma
said.
Geron cultivates its embryonic stem cells differently than
others, he said, adding that no tumors have been seen in animals up to
nine months after injections into the rodents' injured spinal cords.
Moreover, he said, the cells survive and help the animals recover, in
part by secreting special factors that spur new nerve growth around the
injury.