Stem cell research holds great promise for neurological disease. One in three Americans will suffer from diseases of the nervous system ranging from stroke to Alzheimer's disease to epilepsy. Very few treatments for neurological disease exist, in part because of the lack of suitable in vitro models with which to test therapeutics. In addition, many neuronal disorders, including Parkinson's disease and ALS, are characterized by loss of important subpopulations of neurons. In affected patients, the only way to restore function may be to provide them with replacement neurons. Many researchers are already working on methods to generate replacement neurons from human embryonic stem cells or to generate accurate in vitro models of neurological diseases. Here, we propose to perform the reverse experiment; we aim to generate pluripotent cell lines directly from human neurons by turning on stem cell genes in these cells. Several groups have been able to turn fibroblasts into pluripotent cell lines that resemble embryonic stem cells using viral infection of the differentiated cells. Once we have generated these lines, we can determine whether they serve as better models for human neurological disease than neurons derived from the few human ES cell lines now available for research. If successful, this novel method should allow us, and other researchers, to generate the best possible in vitro models for a wide range of human neurological diseases.
Statement of Benefit to California:
The goal of this study is to develop a novel method to generate stem cell lines directly from neurons, which is currently impossible in humans. Our findings will also allow us to validate or improve current strategies to generate replacement neurons from human embryonic stem cells. Our experiments should suggest new ways to derive patient specific cell lines to treat or study common human neurological diseases such as Alzheimer's and autism. These findings may lead to relief for patients who suffer from currently untreatable diseases of the nervous system and our method could be widely used by researchers throughout California. In addition, our novel methods may foster innovation in the dynamic biotechnology and health-care sectors of the California economy, which would benefit many Californians in by creating jobs and promoting economic growth.