WSJ.com - Stem-Cell Aid May Soon Treat Some Blindness

The Wall Street Journal

September 23, 2004

HEALTH


Stem-Cell Aid
May Soon Treat
Some Blindness

By SHARON BEGLEY
Staff Reporter of THE WALL STREET JOURNAL
September 23, 2004; Page B1

Amid the political debate over whether and when embryonic stem cells
might prove medically useful, scientists today are announcing a
laboratory advance
they say could soon lead to human tests of a stem-cell treatment for two
common forms of blindness.

In a paper to be published in the fall issue of the journal Cloning and
Stem Cells, and posted on that journal's Web site today, scientists
describe experiments
in which they grew human embryonic stem cells that developed into
specialized cells of the human eye. The research involved both stem
cells approved for
research by President Bush as well as some from a private lab that are
off-limits to federally funded researchers.

The specialized eye cells, called retinal pigment epithelium cells, are
crucial for vision because they provide nutrients to and eliminate waste
from the
rods and cones -- the eye's light receptors. When the RPE cells
deteriorate, so do the rods and cones, leading to diseases such as
age-related macular
degeneration, a progressive disease that is the leading cause of
blindness in people over 50. There is no good treatment for the disease,
which afflicts
an estimated nine million Americans.
[ ]

"Retinal-cell transplants could be one of the first applications of
human embryonic stem-cell technology," says one of the study's leaders,
Robert Lanza,
medical director of Advanced Cell Technology, a closely held
biotechnology company in Worcester, Mass. "With the right resources, we
hope to get this into
the clinic in one to two years."

That goal may be overly optimistic, because the retinal cells grown from
embryonic stem cells haven't been tested on animals, let alone on
people, to determine
if they are both safe and effective in restoring vision. Such tests
could take five years.

Advanced Cell has scored several notable firsts -- its scientists were
the first to clone an endangered species, the cow-like gaur, which died
soon after
birth. It has also been aggressive in trumpeting its achievements. In
2001, for instance, the company reported it had cloned a human embryo,
but the embryo
failed to develop beyond the six-cell stage. Advanced Cell is currently
seeking to raise money through a private placement.

Scientists who weren't involved in the retinal-cell study, but who have
reviewed it, were nevertheless impressed. "This is a very important
step," says
Sally Temple of Albany (N.Y.) Medical College, a leading expert in
neuronal stem cells. "The work being reported is sound; these are
unequivocally RPE
cells. This seems to be a very promising use of embryonic stem cells."

In large part that's because the eye is much more accessible than the
brain, where cells to replace those lost in Alzheimer's disease or
Parkinson's disease
would have to be transplanted. And unlike brain neurons, the retinal
cells don't have to form complicated connections -- synapses -- with
other cells in
order to function.

"When transplanting RPE cells, wiring is not an issue and access is not
a problem," says Jeff Stern, a retinal surgeon in Albany who has tracked
both animal
and human experiments using transplants of RPE cells to treat blindness.

Stem cells come from days-old embryos and have the potential to develop
into any of the 200-plus kinds of cells found in the human body. In
theory at least,
that makes them a potential source of replacement cells for those
destroyed by diseases such as Parkinson's, juvenile diabetes and
spinal-cord injury.
They are also the focus of an impassioned ethical debate, because in
order to harvest embryonic stem cells, the embryos must be destroyed.

It had been thought that scientists would have to manipulate stem cells
in some way to get them to develop into a desired cell type, such as by
growing
them in a mixture of nutrients containing some sort of
differentiation-inducing molecules. But Dr. Lanza and Advanced Cell's
Irina Klimanskaya found that
the stem cells didn't need any help. While growing in a lab dish, they
spontaneously differentiated -- for reasons that aren't entirely clear
-- first
into neurons and then into the retinal cells.

To the scientists' surprise, the cells were not only indistinguishable
from adult retinal cells, but resembled these cells more closely than do
existing
lines of such cells.

The retinal cells derived from embryonic stem cells could become a
source of replacement cells for people losing their vision to
age-related macular degeneration
or retinitis pigmentosa, which affects an estimated 200,000 Americans,
says Albany Medical College's Prof. Temple.

Transplants to restore vision in animals have been promising. In March,
scientists at Kyoto University Hospital in Japan reported that they had
induced
embryonic stem cells from monkeys to turn into retinal pigment
epithelial cells. When they transplanted those cells into rats with
retinal damage, they
allowed the retina's rods and cones to thrive.

Retinal-cell transplants in people, however, have produced mixed
results. "RPE-cell transplants, some using cells from cadavers and some
from fetuses, have
not been successful in most of the patients," says Marco A. Zarbin,
professor and chair of the Institute of Ophthalmology and Visual Science
at the University
of Medicine and Dentistry of New Jersey, in Newark. In a few cases the
patient's immune system seemed to reject the transplant, while in others
the layer
of tissue that the retinal cells must attach to in order to function was
abnormal, due either to disease or to age.

Transplanted fetal retinal cells seem to stick to that surface, even
when it is old or diseased, better than transplanted adult retinal cells
do, which
raises the hope that retinal cells from embryonic stem cells will too.
In a 1999 study, for instance, 14 patients with retinitis pigmentosa
received fetal
retinal transplants. There was no rejection of the transplant for the 44
months the patients were studied. In five of the patients vision
improved. And
last month physicians in Kentucky reported that they had transplanted a
sheet of fetal RPE and related cells into one eye of a patient with
retinitis pigmentosa.
Her vision improved enough to read large-print magazines.

"There is no sign of rejection and the improvement is real," says Norman
Radtke of Norton Audubon Hospital, Louisville, who performed that
surgery. Dr.
Radtke warns, however, that RPE cells alone mightn't be sufficient to
restore vision; related retinal cells might also be required.

The Advanced Cell team found that all embryonic stem-cell "lines," or
colonies of stem cells being kept alive in a nutrient medium in a lab
dish, aren't
alike. For their experiment, the scientists obtained 11 such lines.
Three were created in 1998 and approved for research by President Bush
in August 2001;
22 such lines are now available, says the National Institutes of Health.
Any stem cells created after that date are off-limits to federally
funded studies.

The Advanced Cell scientists also used six embryonic stem-cell lines
created using private funding by Douglas Melton of Harvard University,
Cambridge, Mass.
Finally, Dr. Lanza's team created stem-cells lines from two blastocysts
-- days-old balls of cells -- donated by couples who had completed
fertility treatment
and had no plans to have the embryos implanted in the woman's uterus.

The White House-approved stem cells didn't differentiate well, Dr. Lanza
says: "We wouldn't have made this discovery if we had been limited to
the stem-cell
lines approved by the president."

Write to Sharon Begley at
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