Aug 25, 2014

Convective forces increase rostral delivery of intrathecal antisense oligonucleotides in the cynomolgus monkey nervous system

bioRxiv
Sune Pletscher-FrankildAjay Verma

Abstract

Background: The intrathecal (IT) dosing route introduces drugs directly into the CSF to bypass the blood-brain barrier and gain direct access to the CNS. We evaluated the use of convective forces acting on the cerebrospinal fluid as a means for increasing rostral delivery of IT dosed radioactive tracer molecules and antisense oligonucleotides (ASO) in the monkey CNS. We also measured the cerebral spinal fluid (CSF) volume in a group of cynomolgus monkeys. Methods: There are three studies presented, in each of which cynomolgus monkeys were injected into the IT space with radioactive tracer molecules and/or ASO by lumbar puncture in either a low or high volume. The first study used the radioactive tracer 64Cu-DOTA and PET imaging to evaluate the effect of the convective forces. The second study combined the injection of the radioactive tracer 99mTc-DTPA and ASO, then used SPECT imaging and ex vivo tissue analysis of the effects of convective forces to bridge between the tracer and the ASO distributions. The third experiment evaluated the effects of different injection volumes on the distribution of an ASO. In the course of performing these studies we also measured the CSF volume in the subject monkeys by Magnetic Resonance Imagin...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Genes
Group III phytoplasma
Cancer Gene Mutation
Human gene
Gene Type
Staging of Disease
Biomedicine
Mutation Abnormality
Gene Flow

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