(Press-News.org) SAN FRANCISCO, CA—June 28, 2012—Scientists at the Gladstone Institutes and an international team of researchers have generated a human model of Huntington's disease—directly from the skin cells of patients with the disease.
For years, scientists have studied Huntington's disease primarily in post-mortem brain tissue or laboratory animals modified to mimic the disease. Today, in Cell Stem Cell, the international team shows how they developed a human model of Huntington's disease, which causes a diverse range of neurological impairments. The new model should help scientists better understand the development of Huntington's—and provide better ways to identify and screen potential therapeutics for this devastating disease.
This new model comes at a time of concentrated federal efforts to accelerate solutions for diseases—including a number of debilitating conditions that touch only small percentages of the population. Last year, the National Institutes of Health consolidated its efforts to attack rare diseases under the new National Center for Translational Sciences.
Huntington's is such a rare disease, although it is the most common inherited neurodegenerative disorder. It afflicts approximately 30,000 people in the United States—with another 75,000 people carrying the gene that will eventually lead to it. Caused by a mutation in the gene for a protein called huntingtin, the disease damages brain cells so that people with Huntington's progressively lose their ability to walk, talk, think and reason.
"An advantage of this human model is that we now have the ability to identify changes in brain cells over time—during the degeneration process and at specific stages of brain-cell development," said Gladstone Senior Investigator Steve Finkbeiner, MD, PhD. "We hope this model will help us more readily uncover relevant factors that contribute to Huntington's disease and especially to find successful therapeutic approaches."
In this research, Dr. Finkbeiner and others took advantage of advanced "reprogramming" techniques pioneered by Gladstone Senior Investigator Shinya Yamanaka, MD, PhD. They reprogrammed skin cells from Huntington's disease patients into stem cells known as induced pluripotent stem cells, or iPS cells—which can become virtually any cell type in the body. The researchers then instructed the iPS cells to develop into neurons, a key type of brain cell. Importantly, each cell line contained a complete set of the genes from each Huntington's disease patient. Because each patient has a different pattern of disease onset and duration, this model may replicate Huntington's more faithfully than animal models do. The model is likely to prove more useful in understanding the disease's progression.
"The iPS cells will provide insights into Huntington's disease, helping us to develop new therapies and test drug candidates," said Dr. Finkbeiner, who is also a professor of neurology and physiology at the University of California, San Francisco, with which Gladstone is affiliated. "We hope that drugs developed with this new human model will have greater success in clinical trials. The track record of animal models for predicting therapies that will work in people has been poor, making drug discovery for neurodegenerative diseases very costly—and therefore less attractive to drug companies. We hope to change that."
INFORMATION:
Other scientists who participated in this research at Gladstone include Julia A. Kaye, PhD, Aaron Daub and Amanda Mason. The consortium research group included investigators at the University of Wisconsin, Cedars-Sinai Medical Center, Massachusetts General Hospital, the University of California, Irvine, the University of Milan, Johns Hopkins University and Cardiff University. Funding for this research came from the National Institute of Neurological Disorders and Stroke. Additional support came from a variety of sources, including the California Institute for Regenerative Medicine, and The Taube-Koret Center for Huntington's Disease Research, The Hellman Family Foundation Alzheimer's Research Program and The Roddenberry Center for Stem Cell Biology and Medicine—all at Gladstone.
About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.
END
Baltimore, MD — In mammals, most lipids (such as fatty acids and cholesterol) are absorbed into the body via the small intestine. The complexity of the cells and fluids that inhabit this organ make it very difficult to study in a laboratory setting. New research from Carnegie's Steven Farber, James Walters and Jennifer Anderson reveals a technique that allows scientists to watch lipid metabolism in live zebrafish. This method enabled them to describe new aspects of lipid absorption that could have broad applications for human health. Their work is published in Chemistry ...
For many grocery shoppers, those perfect, red tomatoes from the store just can't match the flavor from the home garden. Now, researchers at Boyce Thompson Institute for Plant Research at Cornell University, USDA and the University of California at Davis have decoded a gene that contributes to the level of sugar, carbohydrates and carotenoids in tomatoes. (Science, June 29, 2012)
Cuong Nguyen, a Cornell graduate student in plant breeding working at the Boyce Thompson Institute (BTI), along with colleagues at BTI, USDA, UC Davis, Universidad Politecénica de Valencia (Spain), ...
LOS ANGELES (EMBARGOED UNTIL NOON EDT ON JUNE 28, 2012) – 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 ...
Christina Wang, M.D., lead investigator at Los Angeles Biomedical Research Institute (LA BioMed) – one of the leading biomedical research institutes in the country – recently completed a study utilizing a new contraceptive gel that has the potential to be developed as a user controlled chemical birth control agent for males. The gel, which contains testosterone and a synthetic progestin called Nestorone, sharply lowers sperm counts in men with few side effects. The study conducted at LA BioMed and the University of Washington is funded by the National Institutes of Child ...
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 visual information from eyes is sent into the brain unconsciously even if you are not aware. One of examples of unconscious seeing is a phenomenon of "blindsight" [Subjects have no awareness, but their brains can see ] in subjects with visual impairment, caused by the damage of a part of the brain called the visual cortex. Although it is already reported that the patients with damage in the visual cortex, who were not aware of seeing, can walk and avoid obstacles, it was not proved whether this was really blindsight. In this new study, the international collaborative ...
Not lying is regarded as a learned and well-known rule of honesty among 14 and 15-year-olds at Zurich's high schools. Additional theoretical moral knowledge also includes conventional rules of honesty such as not using unfair aids during school tests or forging parents' signatures. What might seem like a duty to live up to school expectations at face value is actually a very different story beneath the surface. After all, dishonest practices are permitted for young people in certain classroom situations and with individual teachers. "In such cases, young people deem it ...
The journal Nature has published a study analysing the lines of arrested growth (LAG) in the bones of around a hundred ruminants, representative of the specific and ecological diversity of that group of mammals. The results show that the presence of these lines is not an indicator of an ectothermic physiology (does not generate internal heat), as had previously been thought, since all warm-blooded mammals have them. The study therefore dismantles the key argument of the hypothesis that dinosaurs could have been cold-blooded reptiles. The work was carried out by researchers ...
A characteristic feature of most animals is their ability to move quickly with the help of their musculature. Animals that can move are able to flee, hunt for prey, travel long distances or conquer new habitats. The evolution of muscles was thus a fundamental step during animal evolution. While the structure and function of muscles, especially of vertebrates, have been intensively studied, the evolutionary origin of smooth and striated muscles has so far been enigmatic. Comparative genome and gene expression studies, performed by researchers Patrick Steinmetz, Johanna Kraus ...
Genetic diversity arises through the interplay of mutation, selection and genetic drift. In most scientific models, mutants have a fitness value which remains constant throughout. Based on this value, they compete with other types in the population and either die out or become established. However, evolutionary game theory considers constant fitness values to be a special case. It holds that the fitness of a mutation also depends on the frequency of the mutation. Scientists from the Max Planck Institute for Evolutionary Biology in Plön and the University of British Columbia ...
