A novel tool that embeds 3Rs principles in multiple sclerosis research.

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The context of the research: Multiple sclerosis (MS) is the most common cause of non-traumatic neurological disability in young adults in Europe and North America. This debilitating disease is modelled in animals by inducing CNS autoimmunity in which the animal's defence system against bacteria and viruses, instead attacks cells in the animal's CNS. This results in experimental autoimmune encephalomyelitis (EAE); a condition characterised by paralysis in the experimental animal. Thus, EAE is classed as severe under the Animals (Scientific Procedures) Act 1986. Although EAE has helped us understand aspects of MS and informed drug discovery and testing, there is an urgent need to find an alternative that eliminates or reduces its use. Here we will develop and verify a cell culture (brain in a dish) model of EAE to replace experiments in living animals.Aims and objectives: With our combined expertise in EAE, myelinating cell cultures, axon degeneration and electrophysiology, we will provide a validated cell culture tool to: * model of EAE/MS using embryonic mice, that (i) reduces the use of EAE by the research and pharmaceutical communities (ii) will be used to generate new concepts, ideas, toxicity screening and target validation and (iii) to investigate how axons are injured and can be rescued in the context of progressive MS.* publicise this model to maximise its uptake * provide training in the 3Rs principles in general, and in the context of understanding, investigating and identifying therapies for neurodegenerative disorders.* instil a long-term appreciation and adoption of the 3Rs principles* elucidate the mechanisms and molecules responsible for axon injury, providing rationale targets for therapeutic intervention* provide mentoring and training in many skills, including adoption of rigorous and unbiased approaches to addressing research questions