Does anyone need more proof that stem cells are not going to serve as universal repair kits for Alzheimer’s disease, Parkinson’s disease, Lou Gehrig’s disease
and spinal cord injury any time soon? Here is what counts as a big
breakthrough in stem-cell research these days: producing cells that can
then be studied for clues to what drugs will work against a particular
disease. I don’t mean to be cynical. Scientists today are announcing what is
truly a milestone: they have taken skin cells from two elderly
women—ages 82 and 89—who have Lou Gehrig’s disease, or amyotrophic
lateral sclerosis (ALS), and used a technique that was announced less
than a year ago to make the cells go backward in time, so to speak, and
become embryonic stem cells. The researchers then made the stem cells
morph into spinal motor neurons, the very ones that die in ALS. It’s a
milestone because earlier studies had generated these induced stem cells
from healthy donors, but no one knew if it would work on cells from
elderly patients with a serious genetic disease. So kudos all around. But the achievement is not, as the press release
puts it, “an important step toward the goal of using induced
pluripotent stem cells . . . to treat disease”—except if the step is
small and the goal is decades away. Just to recap what scientists led by Kevin Eggan of the Harvard Stem Cell Institute and Christopher Henderson of Columbia are reporting online today in Science.
They started with skin cells from the two women, who had an inherited
form of ALS in which one gene is mutated (this mutation is the cause of
only about 2 to 5 percent of ALS cases, however, something to keep in
mind). They then followed the recipe discovered last year, introducing
four genes into the skin cells to “reprogram” them, essentially causing
the cells to revert to embryonic stem-cell status. They then bathed
the "pluripotent" cells in a stew of molecules that caused them to morph
into motor neurons. Voila: motor neurons with the exact same genetic
make-up as the women. Not too long ago, that possibility was hailed as a technique for
producing “patient-specific cells” that could then be returned to the
patient to cure what ailed her. But think about it. The cells carry the
same mutation that causes these women’s ALS in the first place.
Transplanting them into the women would be like putting a cirrhotic
liver into an alcoholic whose own liver was kaput. Sure, maybe the cells could be used to generate genetically-matched
healthy neurons to replace the diseased ones. But in a press conference,
the scientists were quite clear about the more likely next step.
“Because the cells contain the genes that produced the disease [in these
women],” Eggan said, “you can study them in a Petri dish.” Henderson
added, “we don’t understand the disease process, and that is preventing
us from developing cures. But we now have in a culture dish cells with
the same genetic make-up as the ALS patients in the very cells that are
affected by the disease. We’ll see if they degenerate and die faster
than normal cells, and will try to understand the mechanism of the
degeneration process, since it is the mechanism that is the key to a
cure, and will test chemical compounds that might stop the
degeneration.” That may sound like something that should
have been done before, but in fact it has been impossible to isolate the
diseased motor neurons from ALS patients, of which there are about
30,000 in the United States. With a limitless supply of those neurons
thanks to the iPS technique, scientists can both study the disease
process and try everything they can think of to stop it. Eggan had originally hoped to produce
patient-specific stem cells using human eggs, in the process called
therapeutic cloning, or somatic-cell nuclear transfer.
In this technique, scientists remove all the genetic material from the
ovum and replace it with the DNA from the skin cell of a patient. The
fertilized ovum undergoes several cell divisions, yielding stem cells
that the scientists then extract and induce to differentiate into the
motor neurons they want to study. But despite blanketing the Boston area with
ads asking women to donate, he had no takers: women were eager to help,
but when they learned that Massachusetts law prohibits the scientists
from compensating them in any way—not for lost time at work, not for
transportation—they had second thoughts. Women can, of course, be paid
thousands of dollars for donating eggs to infertile couples. “Over the
last two years we’ve done everything we could within the law to recruit
women to donate ova,” Eggan said. “We were never able to recruit enough
donors because we were legally prevented from providing the same sort of
compensation that these women would receive for donating their ova for
in vitro fertilization.” |