Salegio Ernesto A, Campagna Michael V, Allen Philip C, Stockinger Diane E, Song Yuanquan, Hwa Granger G C
1 Valley Biosystems, Inc. , West Sacramento, CA.
2 Raymond G. Perelman Center for Cellular and Molecular Therapeutics , The Children's Hospital of Philadelphia, Philadelphia, PA.
Hum Gene Ther Methods. 2018 Aug;29(4):169-176. doi: 10.1089/hgtb.2018.049. Epub 2018 Aug 13.
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.
本研究利用实时磁共振成像引导的对流增强递送（MRI-CED）技术，探索了将实质内递送（钆特醇和/或5型腺相关病毒载体增强绿色荧光蛋白[AAV5-eGFP]）至非人灵长类动物小脑的可行性。所有动物均耐受神经外科手术，未出现任何临床后遗症。在输注部位的小脑实质内检测到基因表达，并导致神经元细胞体和纤维的转导。组织病理学显示插管通道茎部有局部损伤。这些发现证明了实时MRI-CED将治疗药物递送至小脑的潜力，小脑具有广泛的相互连接，可作为治疗神经疾病的靶点。
