Research at Harvard
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IPS cells as a model for DYT1 Dystonia - Dr. Nutan Sharma and Chis Bragg
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The objective of this research is to establish a collection of DYT1-specific induced pluripotent stem (iPS) cells, which are stem cells derived from patient-donated somatic (skin) cells, and matched controls that will serve as a public resource for the dystonia research community. These cells, which are generated by reprogramming skin fibroblasts resemble embryonic stem cells in culture and can be differentiated into specific cell types, such as neurons, needed for research. Thus, DYT1-specific iPS cells will represent a self-renewing population of cells bearing ‘natural’ levels of the mutated target protein, torsinAΔE, capable of becoming human neurons, which are thought to be critical in developing DYT1 dystonia. This model would enable multiple dystonia research groups to conduct new studies designed to study neuron-specific defects associated with torsinAΔE.
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The current plan is to perform an initial analysis of DYT1 vs. control-derived neurons and publish the findings, at which point the cells will be deposited with the Coriell Institute for public distribution. The Institute has already been notified about the intent to deposit the DYT1 iPS cells.
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Drug Discovery for Dystonia using Chemical Genomics - Dr. Chris Bragg
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Supported by the Dr. Edward V. Staab Memorial Grant Award, Dr. Bragg and his colleagues have managed to complete the proposed expresiion profiling primary DYT1 fibroblasts and controls. In collaboration with Dr. Laurie Ozelius (Mt. Sinai), researchers have managed to extend the expression to a second cell type known as lymphoblasts. After deep analysis and vigor determination, investigations have revealed candidate compounds which may resue the DYT1 cellular state.
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In order to confirm such predictions, additionals steps are being made to find the best compounds needed to move forward into animal models and further pre-clincial development.
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CRISPR Cas9 Alignment Grant II
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The CRISPR Cas 9 alignment grant project is a collaboration project between the institutions: UF, UAB, and Harvard. This project will specifically target the DYT1 gene producing the mutant protein that causes the symptoms of dystonia. The theory is that by introducing a therapy that deletes the genetic code producing the mutation, those with dystonia will stop manufacturing the "bad form" of the Torsin protein and your body will function normally with the "good form" of the protein already being produced.
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