Patient-tailored approach to reprogram human subventricular zone neural stem cells for the development of cell-based therapies to treat motor deficits after stroke
Stroke is a common disease in the United States which leaves many patients with permanent disability.
So far there is no treatment available to recover function after stroke except for physical and occupational therapy. After a recovery period of up to two years, patients do not have any hope of making any further progress.
The proposed research will aim to solve this problem by using stem cells from patients to recover function after stroke. Tissue containing stem cells will be obtained from patients during a routine neurosurgical operation. These stem cells will be reprogrammed in the lab so they can be expanded in vast numbers and then directed to make a subset of neurons which have been lost after stroke.
Derived cells first will be tested in mice to make sure that they do not form cancer or contribute to other adverse events after transplantation. If the safety of the transplantation has been confirmed, derived cells will be tested in animal models for their capacity to recover motor function after injury. The proposed experiments will give us data to apply for IND approval from the Food and Drug Administration to test these cells in stroke patients. Successful integration of the derived cells after transplantation and recovery of motor function would have a major impact on the lives of patients and the research community. So far the deficits after stroke cannot be restored, but we hope to change this with our research and to make a difference in the lives of our patients.
The proposed research will benefit the State of California on two levels:
First, if the grant is awarded, it will create jobs since I am planning on hiring at least one postdoctoral associate and one technical associate. This is thought to be the start of a larger research group which I am planning on building at UC Davis over the next several years. Since California has excellent medical schools and neurobiology programs, I will pay special attention to applications from graduates within the state.
Second, the proposed research is going to benefit the citizens of the State of California if I can show that transplantation of reprogammed neural stem cells can enhance functional recovery after stroke. More than 50% of people with severe stroke are in a nursing home 90 days and 1 year after a stroke, and 70% of patients will have spent some time in a nursing home by 1 year. The proposed reseach is aimed at helping patients who are permanently required to stay in a nursing home to regain motor function after stroke so that they may progress to live more independently and possibly be discharged to a lower level of care. Nursing home stays create a large economic burden in California. Therefore, reducing the number of stays would have a significant impact on the health care system in the state. It would also help citizens taking care of family members to regain hope that the condition of their loved ones is not permanent but in fact amenable to treatment.