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

研究背景：多发性硬化症（MS）是欧洲和北美年轻人非创伤性神经功能障碍的最常见原因。这种使人衰弱的疾病通过诱导CNS自身免疫在动物中建模，其中动物针对细菌和病毒的防御系统攻击动物CNS中的细胞。这导致实验性自身免疫性脑脊髓炎（EAE）;一种以实验动物瘫痪为特征的病症。因此，根据1986年动物（科学程序）法案，EAE被归类为重度。尽管EAE帮助我们了解了MS的各个方面，并为药物发现和测试提供了信息，但迫切需要找到一种消除或减少其使用的替代品。在这里，我们将开发和验证细胞培养目的和目标：凭借我们在EAE、髓鞘细胞培养、轴突变性和电生理学方面的综合专业知识，我们将提供一种经过验证的细胞培养工具，以：* 使用胚胎小鼠的EAE/MS模型，（i）减少研究和制药界对EAE的使用（ii）将用于产生新的概念，想法，毒性筛选和靶点验证，以及（iii）研究轴突是如何受损的，以及在进行性MS的背景下如何获救。宣传这一模型，以最大限度地提高其吸收率 * 提供一般3R原则的培训，并在理解，调查和确定神经退行性疾病治疗方法的背景下提供培训。灌输对3R原则的长期理解和采用 * 阐明轴突损伤的机制和分子，为治疗干预提供合理的目标 * 提供许多技能的指导和培训，包括采用严格和公正的方法来解决研究问题

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