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MR-guided delivery of AAV2-BDNF into the entorhinal cortex of non-human primates.
Nagahara, Alan H; Wilson, Bayard R; Ivasyk, Iryna; Kovacs, Imre; Rawalji, Saytam; Bringas, John R; Pivirotto, Phillip J; Sebastian, Waldy San; Samaranch, Lluis; Bankiewicz, Krystof S; Tuszynski, Mark H.
Afiliación
  • Nagahara AH; Department of Neurosciences, University of California-San Diego, La Jolla, CA, 92093, USA.
  • Wilson BR; Department of Neurosciences, University of California-San Diego, La Jolla, CA, 92093, USA.
  • Ivasyk I; Department of Neurosciences, University of California-San Diego, La Jolla, CA, 92093, USA.
  • Kovacs I; Department of Neurosciences, University of California-San Diego, La Jolla, CA, 92093, USA.
  • Rawalji S; Department of Neurosciences, University of California-San Diego, La Jolla, CA, 92093, USA.
  • Bringas JR; Department of Neurological Surgery, University of California-San Francisco, San Francisco, CA, 94103, USA.
  • Pivirotto PJ; Department of Neurological Surgery, University of California-San Francisco, San Francisco, CA, 94103, USA.
  • Sebastian WS; Department of Neurological Surgery, University of California-San Francisco, San Francisco, CA, 94103, USA.
  • Samaranch L; Department of Neurological Surgery, University of California-San Francisco, San Francisco, CA, 94103, USA.
  • Bankiewicz KS; Department of Neurological Surgery, University of California-San Francisco, San Francisco, CA, 94103, USA. Krystof.Bankiewicz@ucsf.edu.
  • Tuszynski MH; Department of Neurosciences, University of California-San Diego, La Jolla, CA, 92093, USA. mtuszynski@ucsd.edu.
Gene Ther ; 25(2): 104-114, 2018 04.
Article en En | MEDLINE | ID: mdl-29535375
Brain-derived neurotrophic factor (BDNF) gene delivery to the entorhinal cortex is a candidate for treatment of Alzheimer's disease (AD) to reduce neurodegeneration that is associated with memory loss. Accurate targeting of the entorhinal cortex in AD is complex due to the deep and atrophic state of this brain region. Using MRI-guided methods with convection-enhanced delivery, we were able to accurately and consistently target AAV2-BDNF delivery to the entorhinal cortex of non-human primates; 86 ± 3% of transduced cells in the targeted regions co-localized with the neuronal marker NeuN. The volume of AAV2-BDNF (3 × 108 vg/µl) infusion linearly correlated with the number of BDNF labeled cells and the volume (mm3) of BDNF immunoreactivity in the entorhinal cortex. BDNF is normally trafficked to the hippocampus from the entorhinal cortex; in these experiments, we also found that BDNF immunoreactivity was elevated in the hippocampus following therapeutic BDNF vector delivery to the entorhinal cortex, achieving growth factor distribution through key memory circuits. These findings indicate that MRI-guided infusion of AAV2-BDNF to the entorhinal cortex of the non-human primate results in safe and accurate targeting and distribution of BDNF to both the entorhinal cortex and the hippocampus. These methods are adaptable to human clinical trials.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Imagen por Resonancia Magnética / Dependovirus / Corteza Entorrinal / Factor Neurotrófico Derivado del Encéfalo Límite: Animals Idioma: En Revista: Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Imagen por Resonancia Magnética / Dependovirus / Corteza Entorrinal / Factor Neurotrófico Derivado del Encéfalo Límite: Animals Idioma: En Revista: Gene Ther Asunto de la revista: GENETICA MEDICA / TERAPEUTICA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido