Fate and connectivity of HESCs in temporal lobe disorders.
There is great promise in the use of human embryonic stem cells to treat neurodegenerative disorders. However, there are several obstacles that need to be overcome before this replacement therapy can become a reality to treat humans. The proposed research is intended to address some of the fundamental principles underlying migration of human embryonic stem cells into regions of the brain that are most vulnerable to neurodegenerative disorders, such as Alzheimer’s disease. Specifically, we intend to take advantage of an intrinsic migratory route for newborn neurons in the adult rodent brain. Our recent studies have shown that newborn neurons arise in the wall of the lateral ventricle and migrate caudally in the rat where they move into some of the cortical areas that are known to degenerate in Alzheimer’s disease. Thus, we propose experiments that will involve injections of human embryonic stem cells into the origin site of this migratory stream in adult and late-life rats, and determine whether these extrinsic cells have the capability to also migrate into these same brain areas. Because our preliminary data indicate that human embryonic stem cells migrate along this route and survive in adult rats, we plan in the proposed study to determine the rate of migration of the injected human embryonic stem cells. In addition, we propose to assess the phenotype of the migrated human embryonic stem cells in these brain areas using an assortment of labeling methods. The last experiment will be performed to determine whether the migrated cells in these brain areas establish synaptic connections with other neurons underlying their functional integration. Together these proposed studies will provide the basis for future clinical trials that are intended to use human embryonic stem cells to replace/replenish degenerating neurons in the brains of aged patients and those with Alzheimer’s disease.
Benefit to California
In the next decade, the generation of Baby Boomers will be hitting their sixties and seventies, an age when neurodegenerative diseases, such as Alzheimer’s disease, typically strike. The care and well-being of this elderly population will represent a large expense for the State of California in the near future. Therefore, the development of innovative treatments will be essential for saving health care costs for the State of California. In addition, any new treatment developed in California will directly benefit the residents by creating new jobs and keeping the state’s healthcare on the leading front of biotechnology. These discoveries made in California will lead to start-up companies creating a new economic stream by their licensing the patents generated from this research. Furthermore, California has obtained a leadership role in this field by being the first state in the USA to support Stem Cell Research. Studies such as those proposed in this grant application will lead to the use of human embryonic stem cells for replacement therapy for patients with Alzheimer’s disease. Once these treatments are developed, citizens of the USA will have to travel to California to obtain these new surgical treatments, leading to more business for the doctors and hospitals in California. In summary, California will benefit from this work through cutting edge research, better health care for its aging population, and more jobs and tax revenue resulting from the creation of these new therapies.