NIH funds effort to develop disease models for pathogenesis and drug discovery
The National Institutes of Health (NIH) has awarded a "Grand Opportunity" grant of $3.7 million to a consortium formed with the Gladstone Institute of Neurological Disease (GIND) and the Taube-Koret Center for Huntington's Disease Research to use stem cell technology to better understand Huntington's disease (HD) and to develop potential therapies. The consortium comprises a partnership of five leading Huntington's research laboratories at the University of Wisconsin, Massachusetts General Hospital, the University of California at Irvine, Johns Hopkins and the Gladstone Institutes. The consortium will use induced pluripotent stem (iPS) cell technology pioneered by Gladstone and Kyoto University's Shinya Yamanaka, MD, PhD, to develop human neurons with Huntington's disease characteristics. iPS technology enables stem cells to be generated from skin samples from adults and avoids the ethical issues surrounding the use of fetal stem cells.
"One of the challenges of Huntington's (and many other neurological diseases) is that many of the potential therapies that show promise in animal models are ineffective in people. We think that molecular differences between mice and humans may be an important cause for this failure," said Steven Finkbeiner MD, PhD, consortium co-leader and Director of the Taube-Koret Center for Huntington's Disease Research and Associate Director of GIND.
"One of the promises of iPS technology is to be able to develop models from Huntington's disease patients that can give us more detailed information about the disease and better predict how therapies could work in humans," he said.
HD, which is also called "Huntington's chorea" and "Woody Guthrie's disease," is a devastating inherited, degenerative brain disorder. More than 100,000 Americans and more than 10 times that number worldwide have HD or are at risk of inheriting the disease from a parent.
iPS cells are generated by reprogramming adult cells from skin or other tissues. They are almost identical to human embryonic stem cells with the ability to self-renew for long periods and to differentiate into all cell lineages. More importantly, iPS cells can be generated from adult patients with genetically inherited and sporadic diseases making it possible to study some diseases, such as Alzheimer's and Parkinson's disease, for which the causes remain largely unknown.
"HD is caused by a single mutation, which provides an ideal paradigm to generate a panel of patient-specific lines," Finkbeiner explained. "This offers hope that these models can teach us why some patients experience certain symptoms and why some family members develop symptoms later rather than sooner, which then can potentially be used to develop treatments that can act before symptoms appear."
Finkbeiner added, "the convergence of a dedicated, collaborative group of committed investigators targeting HD, the need for new treatments based on the root causes of the disease, and the emergence of powerful new technologies herald a truly grand opportunity to make a real difference for those afflicted with Huntington's."
Dr. Finkbeiner's primary affiliation is with the Gladstone Institute of Neurological Disease where his laboratory is located and all of his research is conducted. He is also associate professor of neurology and physiology at the University of California, San Francisco.
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