NYT article about stem cells, brain disease cures.
May 30, 2000
Neural Cells, Grown in Labs, Raise Hopes for
Brain Disease Cures
By ANDREW POLLACK
Sylvia Elam saw the benefits of her
operation as soon as she was
wheeled into the recovery room
and ate lunch. For the first time in years,
she could taste the food.
After a stroke in 1993, Mrs. Elam, of
Scottsdale, Ariz., lost most of the
movement and sensation on her right side.
But last year she became one of the first
people in the world to have cells
manufactured in a laboratory implanted
into her brain. The implant enabled Mrs.
Elam, now 66, to talk again without
stammering, to throw a ball with her right
arm, to walk somewhat without a cane
and even to drive a car.
"It was absolutely beyond our wildest
dreams," said Mrs. Elam's husband, Ira.
Not all cases have had such positive
results, but hope is growing that neural
cells implanted into the brain can replace
damaged cells and restore functions lost
to stroke, spinal cord injury or
neurological diseases like Parkinson's and
Alzheimer's, most of which have no
effective treatments.
"It's almost like reseeding your lawn," said
Dr. Evan Y. Snyder, a neurologist at
Children's Hospital in Boston and at
Harvard Medical School, who has
successfully used the technique to treat
rats with a disease similar to multiple
sclerosis.
In Mrs. Elam's case, a few months after
the operation she suffered setbacks as a
result of a second, apparently unrelated,
stroke.
The quest to restore the neural
connections in the brain has been spurred
by two recent scientific developments.
One was the isolation of so-called stem
cells, the primordial cells from which all
others evolve, that can potentially be made
into neural cells for transplantation.
In addition, in tests conducted in animals,
the cells have had the ability to migrate
through the brain to where they are
needed to repair damage.
A second development was the discovery
that adult brains continue to produce new
cells, overturning conventional wisdom
that brain cells are not replenished. This
suggests some capacity for nervous
system regeneration.
The discoveries have set off a race by
companies hoping to develop cells to be
sold for neural transplantation, part of the
larger field of regenerative medicine. But
harnessing such cells will require
negotiating a minefield not only of
technical challenges but of ethical ones,
since most stem cells come from either
embryos discarded by fertility clinics or
aborted fetuses.
Some scientists and business executives
worry that the neural implant field will
repeat the history of gene therapy, which
has gone through 10 years of largely
dashed hopes, controversial clinical trials
and burned investors, though there have
been some recent signs of success.
"We would do well to learn the lesson
from the troubled path of the gene therapy
field: not to promise too much too early," wrote Anders Bjorklund and Olle
Lindvall, Swedish scientists, in a commentary in the June issue of Nature
Neuroscience.
They said they see signs of a rush toward "ill-founded clinical trials" without
adequate scientific rationale.
Still, the two scientists have been implanting brain tissue from aborted human
fetuses into the brains of people with Parkinson's disease, which causes a
loss of motor skills, for almost a decade. In some patients the treatment has
caused a slight improvement in motor control, which has lasted 5 to 10
years.
But such treatment, which has also been done in this country, requires
several fetuses for each patient. Moral questions notwithstanding, there are
simply not enough fetuses to treat this nation's million or more Parkinson's
patients.
So scientists are searching for cells that can be mass produced -- "neurons in
a bottle," said George W. Dunbar Jr., acting chief executive officer of
StemCells Inc., in Sunnyvale, Calif., one of the companies pursuing the
treatments.
The cells implanted in Mrs. Elam were supplied by Layton BioScience Inc.,
also of Sunnyvale, and derived from testicular cancer cells isolated from a
patient in the 1970's. Scientists found, almost serendipitously, that when
treated with chemicals called retinoids, some of the cells turned into neural
cells. Six of the 12 stroke patients treated with the cells had some
improvement in motor skills, said Dr. John Kondziolka, the University of
Pittsburgh neurosurgeon who performed the operations.
Similar hints of success have been found in clinical trials run by Diacrin Inc.
of Charlestown, Mass., the company furthest along in neural cell implants. It
harvests brain cells from pig fetuses, which have been used to treat more
than 20 Parkinson's patients and several with stroke, Huntington's disease and
epilepsy.
But there are fears the cancer-derived cells could cause cancer and that cells
from pigs could infect patients with animal viruses.
Diacrin recently suspended its trials on stroke victims after two of five
patients suffered seizures, though the company does not think the pig cells
were the cause. While Layton and Diacrin say their cells are safe, some
experts think they will eventually be replaced by alternatives that are less
unappealing to patients.
That would mean human stem cells, which can be grown in great quantities.
The greatest excitement revolves around so-called embryonic stem cells,
which were first isolated in 1998 by Dr. James Thomson of the University of
Wisconsin. These cells can turn into virtually any cell in the body -- including
the liver, kidney, blood or heart, as well as neurons.
But such cells are at the center of an ethical controversy, with opponents
saying it is immoral to use embryos for medical purposes.
By law, federal money cannot be used for research involving the destruction
of embryos.
The National Institutes of Health has proposed new guidelines to allow
scientists receiving its money to work with the cells, provided that the cells
are created with private money.
Senators Arlen Specter, Republican of Pennsylvania, and Tom Harkin,
Democrat of Iowa, have proposed a bill that would ease the restrictions. But
abortion opponents remain opposed to any such relaxation.
The research ban does not affect scientists with corporate financing, which
has allowed companies to dominate the field.
Geron Corporation of Menlo Park, Calif., which financed the work at
Wisconsin, has commercial rights to the embryonic stem cells.
It also has the patent rights to a similar type of primordial cell isolated by Dr.
John Gearhart of Johns Hopkins University, also with Geron financing.
Other companies, looking to sidestep both Geron's patents and the ethical
issues surrounding embryonic cells, are using so-called neural stem cells on
which they have obtained patents. These are less versatile than embryonic
stem cells. They can turn into different types of neural cells but probably not
into others, like kidney or liver cells.
But those working with neural stem cells say that might even be an advantage
for treating a neurological disease. Embryonic stem cells "turn into bone cells
and knee cells," said I. Richard Garr, president and chief executive of
NeuralStem Biopharmaceuticals Ltd. of College Park, Md.
"You can't put them in a person's head without being 100 percent sure they
won't turn into these other things."
Dr. Thomas B. Okarma, president and chief executive of Geron, countered
that embryonic cells could more easily be multiplied and made to live forever
than the neural stem cells, providing an endless supply. "The more upstream
you start, the more total control," he said.
In neural stem cells, NeuralStem is competing with StemCells Inc., a publicly
traded company that was known as CytoTherapeutics Inc. until it abandoned
its previous business to focus on stem cells. Layton, which made the cells
used on Mrs. Elam, has now also moved into neural stem cells by obtaining
from Children's Hospital in Boston a license for a line of cells developed by
Dr. Snyder.
The other companies also have strong scientific credentials. NeuralStem was
founded by scientists from the National Institutes of Health laboratory of Dr.
Ronald McKay, a pioneer in neural stem cells.
StemCells counts among its scientific advisers Dr. Irving L. Weissman, a
stem cell expert at Stanford, and Dr. Fred H. Gage of the Salk Institute for
Biological Sciences, who made some of the crucial discoveries that the adult
brain can grow new cells.
Other companies in the emerging field include ReNeuron Ltd. in London and
Neuronyx of Malvern, Pa., which is headed by Hubert Schoemaker, the
former chief executive of Centocor, a leading biotechnology company now
owned by Johnson & Johnson.
The neural stem cells are not free of ethical controversy, since they generally
come from fetuses. But the companies say that since they can multiply the
cells in the laboratory, they might need only a single fetus to supply hundreds
of patients, if not the entire world demand.
"If we had to go back to human fetal material on a continuing basis, that
would be a concern," said Gary L. Snabel, president and chief executive of
Layton. But with only a few fetuses needed for all time, "most people would
say that's not an unreasonable strategy."
The recent discoveries that adult brains still contain some stem cells makes it
possible to derive such cells from adults, which would remove the ethical
questions. But the scientists say the fetal cells are easier to obtain and easier
to grow and that adult stem cells might lack the resiliency of the embryonic
or fetal ones.
There are still many technical problems to overcome with both neural stem
cells and embryonic stem cells, and it could be several years before clinical
trials begin.
The biggest challenge is trying to get the stem cells to reliably turn into a
single desired type of cell, which is usually done by exposing the cells to
certain growth factors or implanting particular genes in them. This cannot be
done yet for embryonic stem cells, though there has been progress.
Dr. McKay of the health institutes has turned mouse embryonic stem cells
into neural cells that produce dopamine, the chemical lacking in patients with
Parkinson's.
Another approach is to use drugs to try to stimulate the brain to grow its own
new cells.
Harry M. Tracy, publisher of Neuroinvestment, an investment newsletter in
Rye, N.H., that follows the neurological medicine companies, said some of
the drugs might reach the market before stem cell implants. Still, he said, a
combination of both approaches would probably be needed.
Copyright 2000 The New York Times Company |
