Huntington's Research Tool Developed Using Stem Cells

By LizaAVILA

Main Category: Huntingtons Disease Also Included In: Stem Cell Research Article Date: 28 Jun 2012 - 9:00 PDT

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Cedars-Sinai scientists have joined with expert colleagues around the globe in using stem cells to develop a laboratory model for Huntington's disease, allowing researchers for the first time to test directly on human cells potential treatments for this fatal, inherited disorder.

As explained in a paper published June 28 on the Cell Stem Cell website and scheduled for print in the journal's Aug. 3 issue, scientists at Cedars-Sinai's Regenerative Medicine Institute and the University of Wisconsin took skin cells from patients with Huntington's disease and reprogrammed them into powerful stem cells; these were then made into the nervous system cells affected by the disease. Seven laboratories around the world collaborated to demonstrate the cells had hallmarks of Huntington's.

"This Huntington's 'disease in a dish' will enable us for the first time to test therapies on human Huntington's disease neurons," said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute and a senior author of the study. "In addition to increasing our understanding of this disorder and offering a new pathway to identifying treatments, this study is remarkable because of the extensive interactions between a large group of scientists focused on developing this model. It's a new way of doing trailblazing science."

The Huntington's Disease iPSC Consortium united some of the world's top scientists working on this disease. Cedars-Sinai researchers took skin cells from a several Huntington's patients, including a six-year-old with a severe juvenile form of the disease. They genetically reprogrammed these tissues into induced pluripotent stem cells, which can be made into any type of cell in the body. The cells lines were banked by scientists at Cedars-Sinai and scrutinized by all consortium members for differences that may have led to the disease. These cell lines are now an important resource for Huntington's researchers and have been made available via a National Institutes of Health-funded repository at Coriell Institute for Medical Research in New Jersey.

Huntington's, known to the public, for example, as the cause of folksinger Woody Guthrie's death, typically strikes patients in midlife. It causes jerky, twitching motions, loss of muscle control, psychiatric disorders and dementia; the disease ultimately is fatal. In rare, severe cases, the disorder appears in childhood.

Researchers believe that Huntington's results from a mutation in the huntintin gene, leading to production of an abnormal protein and ultimately cell death in specific areas of the brain that control movement and cognition. There is no cure for Huntington's, nor therapies to slow its progression.

The consortium showed Huntington's cell deficits or how they differ from normal cells, including that they were less likely to survive cultivation in the petri dish. Scientists tried depriving them of a growth factor present around normal cells, or "stressing" them, and found that Huntington's neurons died even faster.

"It was great that these characteristics were seen not only in our laboratory, but by all of the consortium members using different techniques," said Virginia Mattis, a post-doctoral scientist at the Cedars-Sinai Regenerative Medicine Institute and one of the lead authors of the study. "It was very reassuring and significantly strengthens the value of this study."

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Huntington's Research Tool Developed Using Stem Cells

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