Mice With Sickle Cell Cured by New Stem Cell Method (Update1)

By Rob Waters
Dec. 6 (Bloomberg) -- A new method of turning ordinary skin cells into
powerful multipurpose cells without destroying embryos has cured its first
patients -- a group of mice with sickle cell anemia.
Researchers took cells from tails of the mice and injected four genes into
them, reprogramming the cells to an embryonic state able to turn into
virtually any cell in the body. The genetic defect that causes sickle cell
was corrected and the stem cells were turned into healthy blood cells, then
inserted into sick mice. The mice became healthy.
It was the first demonstration that the process may be used as a therapy.
Sickle cell anemia affects some 70,000 people in the U.S. and millions of
people around the world. In humans, the method may lead to individualized
treatments using a patient's own skin cells, to ensure the cells aren't
rejected.
``To use this reprogramming for patient-specific therapy, you have to
demonstrate you can really correct a major genetic disease, and that's what
we do here,'' said Rudolf Jaenisch, a stem cell researcher at the Whitehead
Institute of the Massachusetts Institute of Technology in Cambridge. His
study was published today in the journal Science.
Sickle Cell
Jaenisch and his colleagues followed a process first developed by Shinya
Yamanaka of Kyoto University in Japan, who succeeded in making it work last
year in mice cells and this year with human cells. By making multipurpose
stem cells without using human eggs or embryos, the process avoids the
ethical controversy that has dogged embryonic stem cell research and led
President George W. Bush to severely restrict federal funding.
The Jaenisch team worked with mice that had been genetically engineered to
have a form of sickle cell anemia, a disease that in the U.S. affects mostly
African Americans. Some 2 million people in the U.S. have sickle cell trait,
a milder form of the condition.
People with the full-blown disease have red blood cells that are shaped like
a sickle, or the letter ``C,'' instead of being round and smooth.
Sickle-shaped cells can't flow easily through the blood stream and tend to
clump and get stuck, keeping a fresh supply of oxygen from getting to all
parts of the body and causing pain, infections and organ damage.
While there are a number of treatments for the disease which can alleviate
its symptoms, there are no cures.
The genetically engineered mice used in the study were ``just as sick as
humans,'' Jaenisch said in a telephone interview yesterday. ``They die
early, they lose weight and have all the problems humans would have.''
Reprogramming Cells
Initially, Yamanaka used four genes to reprogram the skin cells, including
one called c-Myc that's known to trigger the formation of tumors. In a paper
released last week, Yamanaka showed it could be done with only three genes,
eliminating the cancer-causing c-Myc.
Jaenisch and his colleagues used all four genes in the first steps of his
process, but then deleted c-Myc. Once they had reprogrammed the mice's skin
cells to a multipurpose state, they followed a known process for inducing
them to become blood cells. The researchers irradiated the mice to wipe out
their defective blood system, and replaced it with the genetically corrected
blood progenitor cells. The mice then had a blood supply free of sickle
cells.
The experiment demonstrates that such a process has the potential to be used
in humans with blood diseases such as sickle cell or leukemia, Jaenisch
said. He estimates it would take two to three months to go through all the
steps of manipulating and reinserting the cells in humans, making it a
viable therapy for such patients.
Hurdles
Still, he says, a number of hurdles must be overcome before the process can
be tried in humans.
Scientists must figure out a way to replace the viruses used to ferry the
genes with a safer mechanism. Viruses can insert themselves permanently in
the genetic structure of the recipient and might trigger cancer or other
disorders.
Jaenisch, like other researchers working on this process, expressed
confidence that scientists will find a way to do this and that the technique
will ultimately be usable in humans.
``If I were to select a disease that would most likely succeed first, it
would be some blood disease,'' Jaenisch said. ``I would not make a
prediction when, but I think it will be sooner than we think.''
To contact the reporter on this story: Rob Waters in San Francisco at
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Last Updated: December 6, 2007 14:53 EST

Rayilyn Brown
Board Member AZNPF
Arizona Chapter National Parkinson's Foundation
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