Replacing, Refining, and Reducing Animal Usage in Epilepsy Research Using a Non-Sentient Model

癫痫是一种慢性疾病，患者经常会经历使人衰弱的癫痫发作，极大地影响他们的生活质量。全世界至少有4000万人（欧洲有600万人）患有癫痫。它不仅对个人而且对社会都有巨大的影响-2004年欧洲癫痫的估计总费用是多少？15.5亿目前对癫痫的科学研究几乎完全使用实验室动物。这些动物实验，主要是在小鼠中进行的，导致1963年意外发现Epilim作为控制癫痫发作的有效药物，Epilim现在是世界上最广泛的癫痫治疗药物。令人惊讶的是，这种药物如何控制癫痫发作尚不清楚，这阻碍了科学家开发更有效的治疗方法或减少副作用的治疗方法。目前，每年有数千只小鼠被杀死用于癫痫实验。我们最近测试了一种简单的单细胞生物（阿米巴，网骨藻），用于替代癫痫研究中的动物。在这些研究中，我们已经确定了Epilim在调节细胞信号传导的关键过程中的一种新作用-通过减少细胞内化学物质家族的处理。已知这些化学物质控制癫痫中过度激活的许多细胞功能，因此这种作用可能涉及癫痫控制。我们还证实了这些实验与癫痫控制有关，因为我们已经在小鼠中测试了一种在网骨藻中鉴定的药物，并显示这种新药比Epilim具有更好的癫痫控制效果。因此，这里概述的项目将开发Dictyosteoblastoma作为癫痫研究的模型。该模型将用于确定新的癫痫治疗方法，并了解药物作用的基础，然后在动物模型中测试少量的先导化合物。最终化合物将在改良的慢性癫痫发作模型中进行测试。因此，该项目将开发一种简单的模型，以取代和减少癫痫研究中的小鼠，并改进长期癫痫控制实验。我们估计，在这个项目中，筛选40种化合物将需要100只动物，减少3900只动物在这些药物的开发中的使用。该项目极有可能有助于解开Epilim在人类中阻止癫痫的复杂方式，并开发新的癫痫治疗方法。

Epilepsy is a chronic medical condition, whereby patients experience often debilitating seizures, greatly affecting their quality of life. At least 40 million people worldwide (6 million people in Europe) have epilepsy. It has a tremendous impact not only to the individual but also to society - the estimated total cost of epilepsy in Europe in 2004 was ?15.5 billion. Current scientific research into epilepsy almost exclusively employs laboratory animals. These animal experiments, primarily in mice, lead to the accidental discovery of Epilim in 1963 as an effective drug in seizure control, and Epilim is now the most widely prescribed drug for epilepsy treatment worldwide. Surprisingly, how the drug works in controlling seizures is unclear, and this has blocked scientists from developing more effective treatments or treatments with reduced side effects. Currently, thousands of mice are killed annually for epilepsy-based experiments.We have recently tested a simple, single celled organism (an amoeba, Dictyostelium) for use in replacing animals in epilepsy research. In these studies, we have identified a novel effect of Epilim in regulating a critical process in how cells signal - by reducing the processing of a family of chemical within cells. These chemicals are known to control a number of cellular functions that are over-activated in epilepsy, thus this effect is likely to be involved in epilepsy control. We have also confirmed that these experiments are related to epilepsy control since we have tested one drug identified in Dictyostelium in mice and show the novel drug has better seizure control effects than Epilim. The project outlined here will thus develop Dictyostelium as a model for epilepsy research. The model will be used to identify new epilepsy treatments and to understand the basis for the drug action, and then test a small number of lead compounds in animal models. Final compounds will be tested in refined chronic seizure models. This project will therefore develop a simple model to replace and reduce and mice in epilepsy research, and refine experiments on long-term seizure control. We estimate that in this project, screening 40 compounds will need 100 animals, reducing animal usage in the development of these drugs by 3900. The project is highly likely to help to unravel the complex way in which Epilim stops epilepsy in the human population and to develop new treatments for epilepsy.