Progress is reported on Parkinson's Disease
By: Nicholas Wade
NY Times, June 21, 2002
Scientists working with human
embryonic stem cells have converted them into the type of brain cell that
is lost in Parkinson's disease, and have shown that the equivalent cells
in mice alleviate Parkinson-like symptoms in rodents.
"What we are showing here is
that we absolutely, definitely have the right cell," said Dr. Ron
McKay, a stem cell biologist who works at the National Institutes of
Health.
The cells produce a
neuron-to-neuron signaling chemical called dopamine. The loss of dopamine
is believed to cause many of the symptoms of Parkinson's disease. Dr.
McKay hopes that the cells he has developed will one day be used to treat
the disease, after he has spent two years testing how they work in
monkeys. Indeed a surgeon could put them in patients quite quickly
"but they wouldn't know what they have done," Dr. McKay said.
The need for caution is apparent
in his own experiments, in which he injected the dopamine-producing mouse
cells into the brains of rats. The dopamine-producing cells on one side of
the rats brains had previously been destroyed with a special chemical. So
the rats, suffering Parkinsons-like effects on one side of their brains,
tended to move in circles.
In the article published today in
Nature, Dr. McKay and his colleagues describe how they injected their
dopamine-producing cells into the damaged sides of the rat brains. The
cells wired themselves up to other cells in the brain and behaved just
like dopamine-making cells, helping the rat's walking behavior.
Unfortunately the cells produced
too much dopamine and instead of straightening the rats out made some of
them walk clockwise instead of counter-clockwise.
Dopamine-making cells obtained
from aborted fetuses have also been used to treat Parkinson's disease, so
far with minor effects.
Dr. Gerald D. Fischbach, a
leading neurobiologist at Columbia University, said that the new cell
therapy approach to Parkinson's was "extremely promising." The
previous studies with fetal cells had shown "a modest improvement in
rigidity and paucity of movement," and Dr. McKay's approach held the
promise of a purer population of cells, Dr. Fischbach said.
Dr. McKay and others have shown
previously that embryonic cells could be converted into dopamine-making
cells, but this is the first time the cells have been implanted in an
animal, with evidence of a functional effect. "So it a step in the
right direction," said Dr. Fred Gage, a brain cell expert at the Salk
Institute.
Critics of cell therapy have
warned that whatever unknown cause kills a Parkinson's patient's
dopamine-producing cells in the first place may also obliterate implanted
cells, however well they work.
But Dr. Sean Morrison, a stem
cell biologist at the University of Michigan, said there was evidence that
90 percent of the risk of Parkinson's comes from an environmental source,
perhaps a one-time exposure to some unknown toxin.
If so, the replacement cells
would not necessarily be destroyed. "I am very optimistic on the
future of transplantation therapies for Parkinson's, but a lot of work is
needed to straighten out the kinks," Dr. Morrison said.
Dr. McKay's recipe for
dopamine-making cells draws on the extensive knowledge that biologists
have now accumulated about the genes that switch on and off in various
groups of cells in the developing embryo.
To mature the cells, he exposes
them to potent signalling factors with names like sonic hedgehog and
fibroblast growth factor-8. He also inserts a gene called Nurr1 whose
product is an internal switching signal that makes cells of the mid-brain
turn into dopamine-making cells.
In terms of a cell therapy
treatment for Parkinson's, Dr. McKay said it would take two years of
experiments with his cells in monkeys and two years to set up a clinical
trial.
Of more immediate use to
patients, he said, was the fact dopamine-making cells could now be made in
profusion and studied in the laboratory. Scientists could hope to
understand better what agents were killing the cells in Parkinson's
patients and what drugs might protect the cells.
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