Biogen

Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0114 - MS Biomarker Discovery: a multi-modal approach to identify biomarkers of myelin repair by leveraging a preclinical rodent model of MS (ID 485)

Speakers
Presentation Number
P0114
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Analysis of remyelination and repair therapies in preclinical models for Multiple Sclerosis (MS) has historically relied mainly on histological examination, which provides limited clinical translatability. To overcome the challenge, we aimed to set up preclinical models, initiated with the cuprizone demyelination model, and to integrate multi-modal longitudinal biomarker evaluations.

Objectives

Employ multi-modal biomarker approaches to longitudinally and sensitively monitor myelin changes by leveraging the cuprizone mouse model.

Methods

C57BL/6 male mice are fed with cuprizone diet (demyelinating toxin) for either 4 weeks or 12 weeks followed by recovery for 2 weeks and 4 weeks, respectively. During demyelination and remyeination, animals undergo either MRI or evoked potential recording for structural and functional assessment of myelin. All readouts are assessed in conjunction with histological examination to correlate multi-modal biomarkers for measuring remyelination.

Results

Cuprizone preclinical model of MS was successfully established that reproduced histological changes in myelin content during the remyelination and demyelination phases. MRI based imaging measurements (MTR and T1/T2 ratio) and electrophysiology (transhemispheric and sensory evoked potentials) were highly consistent with cellular level changes in myelin content and correlative with each other. Of interest, during de- and re-emyelination, MTR and T1/T2 demonstrated a reduction and trend to rebound respectively, while DTI was increased and stayed high during the measurement timeframe. Ongoing evaluation to further explore and study the correlation between multiple biomarker modalities and serum neurofilament analyses is underway.

Conclusions

A platform to longitudinally monitor multi-modal biomarkers in the context of demyelination/remyelination in a preclinical model of MS has been established by this study. Ultimately this platform willserve to evaluate efficacy of remyelinating therapeutics by implementing translational biomarkers for faster readouts.

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