@article{discovery10168878,
          volume = {15},
            note = {{\copyright} 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).},
           month = {April},
          number = {4},
            year = {2023},
           title = {Targeted Extracellular Vesicle Gene Therapy for Modulating Alpha-Synuclein Expression in Gut and Spinal Cord},
       publisher = {MDPI AG},
         journal = {Pharmaceutics},
        keywords = {Parkinson's disease; alpha-synuclein; gene therapy; exosomes; spinal cord; intestine},
             url = {http://doi.org/10.3390/pharmaceutics15041230},
        abstract = {The development of effective disease-modifying therapies to halt Parkinson's disease (PD) progression is required. In a subtype of PD patients, alpha-synuclein pathology may start in the enteric nervous system (ENS) or autonomic peripheral nervous system. Consequently, strategies to decrease the expression of alpha-synuclein in the ENS will be an approach to prevent PD progression at pre-clinical stages in these patients. In the present study, we aimed to assess if anti-alpha-synuclein shRNA-minicircles (MC) delivered by RVG-extracellular vesicles (RVG-EV) could downregulate alpha-synuclein expression in the intestine and spinal cord. RVG-EV containing shRNA-MC were injected intravenously in a PD mouse model, and alpha-synuclein downregulation was evaluated by qPCR and Western blot in the cord and distal intestine. Our results confirmed the downregulation of alpha-synuclein in the intestine and spinal cord of mice treated with the therapy. We demonstrated that the treatment with anti-alpha-synuclein shRNA-MC RVG-EV after the development of pathology is effective to downregulate alpha-synuclein expression in the brain as well as in the intestine and spinal cord. Moreover, we confirmed that a multidose treatment is necessary to maintain downregulation for long-term treatments. Our results support the potential use of anti-alpha-synuclein shRNA-MC RVG-EV as a therapy to delay or halt PD pathology progression.},
            issn = {1999-4923},
          author = {Izco, Maria and Schleef, Martin and Schmeer, Marco and Carlos, Estefania and Verona, Guglielmo and Alvarez-Erviti, Lydia}
}