Brain cell transplantation research has shown that structural and functional repair of the adult brain is possible. We are testing the functional hypothesis that embryonic striatal neurons can replace neurons lost in adult primate striatum and improve signs of Huntinton's disease (HD). The lack of an optimal human donor cell source in a clinical scenario has led us to utilize zenogeneic (here transgenic pig) embryonic donor cells. Our preliminary in vivo data show that successful xenografts survival in the primate brain requires immunosuppression by cyclosporine, azathiopirne, methylprednisolone and complement inhibition (CD59 transgenic donor tissue and monoclonal antibodies against complement C5). To test the functional hypothesis, we proposed the following experiments: We will transplant CD59 complement aggregation inhibitor expressing transgenic porcine fetal striatal (E35 LGE) cells to the caudate-putamen of non-human primate (Macaca mulatta) with neuronal loss similar to that seen in HD. To determine how functional recovery depends on survival and growth of porcine striatal transplants, we will collect physiological in vivo data by PET/MRI/MRS and behavioral data by examining motor and cognitive function. The physiological analysis of LBE graft function by in vivo imaging and behavioral assays is followed by detailed morphological studies. Combine, these studies will provide essential data on the relationship between structural and functional integration of embryonic neuronal xenografts in a HD primate model. These experiments will improve our knowledge of basal ganglia function and plasticity, as well as determine parameters for optimal cell transplantation in patients with neurological disease.
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