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MEDICAL: Turning skin Cells into Brain cells

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MEDICAL: Turning skin Cells into Brain cells

Post by Naseem Abbas Malik on Sun Jul 01, 2012 6:29 am

Johns Hopkins researchers, working with an international consortium,
say they have generated stem cells from skin cells from a person with a
severe, early-onset form of Huntington's disease (HD), and turned them
into neurons that degenerate just like those affected by the fatal
inherited disorder. By creating "HD in a dish," the researchers say they
have taken a major step forward in efforts to better understand what
disables and kills the cells in people with HD, and to test the effects
of potential drug therapies on cells that are otherwise locked deep in
the brain.

Although the autosomal dominant gene mutation responsible for HD was
identified in 1993, there is no cure. No treatments are available even
to slow its progression.

The research, published in the journal Cell Stem Cell, is
the work of a Huntington's Disease iPSC Consortium, including scientists
from the Johns Hopkins University School of Medicine in Baltimore,
Cedars-Sinai Medical Center in Los Angeles and the University of
California, Irvine, as well as six other groups. The consortium studied
several other HD cell lines and control cell lines in order to make sure
results were consistent and reproducible in different labs.

The general midlife onset and progressive brain damage of HD are
especially cruel, slowly causing jerky, twitch-like movements, lack of
muscle control, psychiatric disorders and dementia, and -- eventually --
death. In some cases (as in the patient who donated the material for
the cells made at Johns Hopkins), the disease can strike earlier, even
in childhood.

"Having these cells will allow us to screen for therapeutics in a way
we haven't been able to before in Huntington's disease,"
saysChristopher A. Ross, M.D., Ph.D., a professor of psychiatry and
behavioral sciences, neurology, pharmacology and neuroscience at the
Johns Hopkins University School of Medicine and one of the study's lead
researchers. "For the first time, we will be able to study how drugs
work on human HD neurons and hopefully take those findings directly to
the clinic."

Ross and his team, as well as other collaborators at Johns Hopkins
and Emory University, are already testing small molecules for the
ability to block HD iPSC degeneration.These small molecules have the
potential to be developed into novel drugs for HD.

The ability to generate from stem cells the same neurons found in
Huntington's disease may also have implications for similar research in
other neurodegenerative diseases such as Alzheimer's and Parkinson's.

To conduct their experiment, Ross took a skin biopsy from a patient
with very early onset HD.When seen by Ross at the HD Center at Hopkins,
the patient was just seven years old. She had a very severe form of the
disease, which rarely appears in childhood, and of the mutation that
causes it. Using cells from a patient with a more rapidly progressing
form of the disease gave Ross' team the best tools with which to
replicate HD in a way that is applicable to patients with all forms of
HD.

Her skin cells were grown in culture and then reprogrammed by the lab
of Hongjun Song, Ph.D., a professor at Johns Hopkins' Institute for
Cell Engineering, into induced pluripotent stem cells. A second cell
line was generated in an identical fashion in Dr. Ross's lab from
someone without HD. Simultaneously, other HD and control iPS cell lines
were generated as part of the NINDS funded HD iPS cell consortium.

Scientists at Johns Hopkins and other consortium labs converted those
cells into generic neurons and then into medium spiny neurons, a
process that took three months. What they found was that the medium
spiny neurons deriving from HD cells behaved just as they expected
medium spiny neurons from an HD patient would. They showed rapid
degeneration when cultured in the lab using basic culture medium without
extensive supporting nutrients. By contrast, control cell lines did not
show neuronal degeneration.

"These HD cells acted just as we were hoping," says Ross, director of
the Baltimore Huntington's Disease Center. "A lot of people said,
'You'll never be able to get a model in a dish of a human
neurodegenerative disease like this.' Now, we have them where we can
really study and manipulate them, and try to cure them of this horrible
disease. The fact that we are able to do this at all still amazes us."

Specifically, the damage caused by HD is due to a mutation in the
huntingtin gene (HTT), which leads to the production of an abnormal and
toxic version of the huntingtin protein. Although all of the cells in a
person with HD contain the mutation, HD mainly targets the medium spiny
neurons in the striatum, part of the brain's basal ganglia that
coordinates movement, thought and emotion. The ability to work directly
with human medium spiny neurons is the best way, researchers believe, to
determine why these specific cells are susceptible to cell stress and
degeneration and, in turn, to help find a way to halt progression of HD.

Much HD research is conducted in mice. And while mouse models have
been helpful in understanding some aspects of the disease, researchers
say nothing compares with being able to study actual human neurons
affected by HD.

For years, scientists have been excited about the prospect of making
breakthroughs in curing disease through the use of stem cells, which
have the remarkable potential to develop into many different cell types.
In the form of embryonic stem cells, they do so naturally during
gestation and early life. In recent years, researchers have been able to
produce induced pluripotent stem cells (iPSCs), which are adult cells
(like the skin cells used in Ross's experiments) that have been
genetically reprogrammed back to the most primitive state. In this
state, under the right circumstances, they can then develop into most or
all of the 200 cell types in the human body.

The other members of the research consortium include the University
of Wisconsin School of Medicine, Massachusetts General Hospital and
Harvard Medical School, the University of California, San Francisco,
Cardiff University the Universita degli Studi diMilano and the CHDI
Foundation.

Primary support for this research came from an American Recovery and
Reinvestment Act (ARRA) grant (RC2-NS069422) from the National
Institutes of Health's National Institute of Neurological Disorders and
Stroke and a grant from the CHDI Foundation, Inc.

Other Johns Hopkins researchers involved in this study include Sergey
Akimov, Ph.D.; Nicolas Arbez, Ph.D.; Tarja Juopperi, D.V.M., Ph.D.;
Tamara Ratovitski; Jason H. Chiang; Woon Roung Kim; Eka Chighladze,
M.S., M.B.A.; Chun Zhong; Georgia Makri; Robert N. Cole; Russell L.
Margolis, M.D.; and Guoli Ming, M.D., Ph.D.
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Naseem Abbas Malik
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Re: MEDICAL: Turning skin Cells into Brain cells

Post by Rahat Ameer on Thu Jul 05, 2012 2:18 am

WOW.....ThanX for sharing Naseem.......tooo imp info! Exclamation
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