Targeted Delivery and Tolerability of MRI-Guided CED Infusion into the Cerebellum of Nonhuman Primates

Hum Gene Ther Methods. 2018 Aug;29(4):169-176. doi: 10.1089/hgtb.2018.049. Epub 2018 Aug 13.

Abstract

This study explored the feasibility of intraparenchymal delivery (gadoteridol and/or Serotype 5 Adeno-Associated Viral Vector-enhanced Green Fluorescent Protein [AAV5-eGFP]) into the cerebellum of nonhuman primates using real-time magnetic resonance imaging-guided convection enhanced delivery (MRI-CED) technology. All animals tolerated the neurosurgical procedure without any clinical sequela. Gene expression was detected within the cerebellar parenchyma at the site of infusion and resulted in transduction of neuronal cell bodies and fibers. Histopathology indicated localized damage along the stem of the cannula tract. These findings demonstrate the potential of real-time MRI-CED to deliver therapeutics into the cerebellum, which has extensive reciprocal connections and may be used as a target for the treatment of neurological disorders.

Keywords: Cerebellum; MRI; NHP; convection-enhanced delivery.

MeSH terms

  • Animals
  • Cerebellum / metabolism*
  • Convection
  • Dependovirus / genetics
  • Gadolinium / adverse effects
  • Gene Transfer Techniques / adverse effects*
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Heterocyclic Compounds / adverse effects
  • Infusions, Intraventricular
  • Macaca fascicularis
  • Magnetic Resonance Imaging
  • Male
  • Organometallic Compounds / adverse effects

Substances

  • Heterocyclic Compounds
  • Organometallic Compounds
  • gadoteridol
  • Green Fluorescent Proteins
  • Gadolinium