At present, there is no cure for the disease and no treatments are available. These findings open up the possibility of testing treatments for the deadly disorder in a petri dish.
The study is the work of a Huntington's Disease iPSC Consortium, including researchers from the Johns Hopkins University School of Medicine in Baltimore, Cedars-Sinai Medical Center in Los Angeles and the University of California, Irvine, and six other groups.
Huntington's disease is an inherited, deadly neurodegenerative disorder. The onset of HD generally occurs during midlife, although it can also strike in childhood - as in the patient who donated the material for the cells generated in this study. The disease causes jerky, twitch-like movements, lack of muscle control, psychiatric disorders and dementia, and ultimately death.
Christopher 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 lead researchers of the study, explained:
"Having these cells will allow us to screen for therapeutics in a way we haven't been able to before in Huntington's disease. 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."
The team are currently testing small molecules for the ability to block HP iPSC degeneration. According to the researchers, these molecules could potentially be developed into new drugs for Huntington's disease.
Furthermore, the teams ability to create "HD in a dish" may also have implications for similar research in other diseases such as Parkinson's and Alzheimer's.
In the study, the team took a skin biopsy from a 7-year-old patient with very early onset of severe HD. In the laboratory of Hongjun Song, Ph.D., a professor at Johns Hopkins' Institute for Cell Engineering, the skin cells were grown in culture and then created into pluripotent stem cells. In addition, a second cell line was created in the same way in Dr. Ross's lab from an individuals without HD.Simultaneously, other HD and control iPS cell lines were generated as part of the NINDS funded HD iPS cell consortium.
Over three months, the researchers converted the cells into generic neurons and then into medium spiny neurons. The team discovered that the medium spiny neurons they created showed rapid degeneration without extensive supporting nutrients. Control cells lines on the other hand, showed no degeneration.
Ross, director of the Baltimore Huntington's Disease Center, said:
"These HD cells acted just as we were hoping. 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."
A variation in the huntingtin gene (HTT) is responsible for the damaged caused by HD. This mutation leads to the production of an abnormal and toxic version of the huntingtin protein. According to the researchers, creating "HD in a dish" is the best way to find out why medium spiny neurons are vulnerable to cell stress and degeneration and to help find a way to prevent HD progressing.
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.
The study was supported by 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.
Written by Grace Rattue