Development of an in vitro screening system to minimise animal use in the search for factors that modulate (re)myelination

Aims

This research aims to develop and optimise an in vitro system for use as a high-throughput screening method to identify novel therapeutic agents which enhance (re)myelination, reducing the number of animals used in the study of neurodegeneration and de-myelinating diseases.

Background

Treatments which enhance, maintain, or restore myelin, are a promising therapeutics for preventing further neurological decline in disorders of the myelin sheath, such as multiple sclerosis.

A number of potential molecular targets have been identified but further progress has been limited as identifying specific treatments is time-consuming, expensive, labour intensive and requires large numbers of animals for research and testing. An in vitro model for screening molecular libraries and identifying potential treatments which enhance myelination could potentially overcome these bottlenecks, and reduce animal use.

Research details and methods

This research will build upon an existing cell culture model of myelination using embryonic mouse spinal cord in order to develop a high throughput screening method. 

The cell culture system will be adapted for use in multi-well formats, 96 or 384 well plates. A robotic system will be established and validated for liquid handling of parameters such as plating and feeding of cell cultures to optimise reproducibility.

To eliminate potential bias in collecting results, an objective automated analysis system will be developed using a high content screening microscope, and template analysis protocols will be developed to quantify effects of myelination.