Standardized Method for Intra-Cisterna Magna Delivery Under Fluoroscopic Guidance in Nonhuman Primates

Hum Gene Ther Methods. 2018 Oct;29(5):212-219. doi: 10.1089/hgtb.2018.041. Epub 2018 Aug 14.

Abstract

Intrathecal delivery of adeno-associated virus vectors and other therapeutics are currently being evaluated for the treatment of central nervous system sequelae of lysosomal storage diseases, motor neuron diseases, and neurodegenerative diseases. As products transition from preclinical to clinical studies, a standardized and clinically relevant method of intrathecal delivery is increasingly germane. Here, we describe a method of intrathecal delivery via suboccipital puncture into the cisterna magna under fluoroscopic guidance in nonhuman primates. This procedure is suitable for use in good laboratory practice compliant studies, has an excellent safety profile, and is highly similar to the procedure currently being explored for use in humans.

Keywords: AAV; central nervous system; gene therapy; intrathecal.

MeSH terms

  • Animals
  • Cisterna Magna / diagnostic imaging*
  • Cisterna Magna / metabolism
  • Dependovirus / genetics
  • Fluoroscopy / methods*
  • Fluoroscopy / standards
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Therapy / standards
  • Injections, Spinal / methods*
  • Injections, Spinal / standards
  • Primates