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• W2614291262 abstract "Therapies capable of decelerating, or perhaps even halting, neurodegeneration in Parkinson’s disease (PD) remain elusive. Clinical trials of PD gene therapy testing the delivery of neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF), have been largely ineffective due to poor vector distribution throughout the diseased regions in the brain. In addition, current delivery strategies involve invasive procedures that obviate the inclusion of early stage patients who are most likely to benefit from GDNF-based gene therapy. Here, we introduce a two-pronged treatment strategy, composed of MR image-guided focused ultrasound (FUS) and brain-penetrating nanoparticles (BPN), that provides widespread but targeted GDNF transgene expression in the brain following systemic administration. MR image-guided FUS allows circulating gene vectors to partition into the brain tissue by noninvasive and transient opening of the blood–brain barrier (BBB) within the areas where FUS is applied. Once beyond the BBB, BPN provide widespread and uniform GDNF expression throughout the targeted brain tissue. After only a single treatment, our strategy led to therapeutically relevant levels of GDNF protein content in the FUS-targeted regions in the striatum of the 6-OHDA-induced rat model of PD, which lasted at least up to 10 weeks. Importantly, our strategy restored both dopamine levels and dopaminergic neuron density and reversed behavioral indicators of PD-associated motor dysfunction with no evidence of local or systemic toxicity. Our combinatorial approach overcomes limitations of current delivery strategies, thereby potentially providing a novel means to treat PD." @default.
• W2614291262 created "2017-05-26" @default.
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• W2614291262 date "2017-05-18" @default.
• W2614291262 modified "2023-10-14" @default.
• W2614291262 title "Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson’s Disease Model" @default.
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• W2614291262 doi "https://doi.org/10.1021/acs.nanolett.7b00616" @default.
• W2614291262 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5539956" @default.
• W2614291262 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28511006" @default.
• W2614291262 hasPublicationYear "2017" @default.
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