Protein production is an early biomarker for RNA-targeted therapies.

ABSTRACT:

Objectives

Clinical trials for progressive neurodegenerative disorders such as Alzheimer's Disease and Amyotrophic Lateral Sclerosis have been hindered due to the absence of effective pharmacodynamics markers to assay target engagement. We tested whether measurements of new protein production would be a viable pharmacodynamics tool for RNA-targeted therapies.

Methods

Transgenic animal models expressing human proteins implicated in neurodegenerative disorders - microtubule-associated protein tau (hTau) or superoxide dismutase-1 (hSOD1) - were treated with antisense oligonucleotides (ASOs) delivered to the central nervous system to target these human mRNA transcripts. Simultaneously, animals were administered ¹³C₆-leucine via drinking water to measure new

SUBMITTER: Self WK 

PROVIDER: S-EPMC6292185 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature