The goal of our work is to understand the mechanisms and pathways that turn undifferentiated human stem or iPS cells into differentiated neurons that can be used in the brain as replacement for neurons lost in neurodegeneration. We will focus on Huntington's disease or chorea (HD), a incurable neurodegenerative disorder that manifests itself first in the middle age. HD is caused by a mutation in the gene, huntingtin, in which an expansion in the CAG coding for glutamine is expanded to above 36 repeats. Huntington’s disease is a dominantly inherited neurodegenerative disorder with massive loss of cells in the striatum- the cell type lost is medium spiny neurons. We will evaluate methods to induce cellular differentiation of ES or iPS into medium spiny neurons. We will also take iPS cells generated from HD skin fibroblasts and develop methods to correct the mutation in the gene huntingtin.
Statement of Benefit to California:
Huntington’s disease is a dominantly inherited neurodegenerative disorder with massive loss of cells in the striatum and replacement of these cells offers a possible therapy. We will use human embryonic stem cells and induced pluripotent stem (iPS) cell technologies with established methods to differentiate stem cells into pure medium spiny neurons and we will develop methods to genetically correct Huntington’s disease iPS cells for use therapeutically in patients.
The studies we perform should benefit the state of California in several ways:
1. We hope to increase the ability to generate medium spiny neurons that can be used in cell-replacement therapies for neurodegenerative diseases such as Huntington’s disease in which loss of these cells correlates with disease. This will directly benefit patients in California and elsewhere.
2. The human embryonic stem cell research we perform may bring new biotechnology jobs to California, thus increasing the state's visibility as a leader in stem cell technology.
3. New biochemical methods for genetically correcting disease iPS cells will have implications for all genetic diseases. Our discoveries could bring revenues to California due to the ability of the state to obtain licensing fees on technology generated using CIRM funds.