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• W2072409944 abstract "Parkinson’s disease (PD), the second most common neurodegenerative disease in the western society, affects more than 1% of the population and its impact on the society increases with the increasing average age. Current treatments for Parkinson disease, based on L-dopa administration, are only symptomatic and the neural loss is not prevented. As a consequence treatments become less effective and lead to the onset of side effects such dykinesia. New treatments are, therefore, highly demanded. New hopes come from the emerging field of gene therapy but its employment for clinical trials has been considerably slowed down due to safety concern regarding its intrinsic irreversibility. In order to circumvent this drawback the availability of a regulatable gene expression system would be favorable. The most widely used gene regulatable system is based on the tet-operon. Despite the good characteristics in gene regulation its employment for treatment in humans is unlikely due to the immunological reactions observed when applied in non-human primate muscle. I this project w propose, for the first time, the employment o the mifepristone-based pSwitch system for regulated gene expression i the CNS b adeno-associated viral (AAV) vectors. The pSwitch system has the advantage t be mainly constituted o human protein components, which should decrease the possibility o an immune reaction against the elements o the system. Moreover, the inducing drug mifepristone i already approved for use i humans. In the first part o the study, using EGFP a reporter gene, the effect o different transcription elements and virus serotypes i evaluated. The aim was t obtain a good compromise between a ideal “zero” level o expression i the off-state and a high level o expression i the on-state. Results obtained here are compared with alternative gene regulatable systems including the tet-system. O c defined the combination o vectors, EGFP was substituted with the neurotrophic factor GDNF and the biological effect o this protein was evaluated i the on- and i the off-states. Using the dopaminergic neuron selective drug 6-OHDA, a rat model o PD was generated. Viruses encoding the pSwitch system for inducible GDNF expression were injected i the area o the lesion and the effect o" @default.
• W2072409944 created "2016-06-24" @default.
• W2072409944 creator A5056956979 @default.
• W2072409944 date "2022-02-20" @default.
• W2072409944 modified "2023-10-14" @default.
• W2072409944 title "A mifepristone-regulated adeno-associated viral vector system for regulated neurotrophic factor expression in the central nervous system." @default.
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