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

癫痫是一种慢性疾病，患者经常经历衰弱的癫痫发作，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年欧洲癫痫的总成本估计为155亿欧元。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身上进行的，导致在1963年意外地发现Epilim是一种有效的癫痫控制药物，现在Epilim是世界上治疗癫痫最广泛的处方药。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，每年有数以千计的小鼠在癫痫实验中被杀。我们最近测试了一种简单的单细胞生物体(一种阿米巴，Dictyostelials)，用于取代癫痫研究中的动物。在这些研究中，我们发现了Epilim在调节细胞如何发出信号的关键过程中的一种新效果--通过减少细胞内一系列化学物质的处理。众所周知，这些化学物质可以控制癫痫中过度激活的许多细胞功能，因此这种作用很可能涉及癫痫控制。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身上测试了一种在Dictyostelius中发现的药物，并表明该新药比Epilim有更好的癫痫控制效果。因此，这里概述的项目将使Dictyostelius成为癫痫研究的模型。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先导化合物。最终化合物将在改进的慢性癫痫模型中进行测试。因此，该项目将开发一种简单的模型来取代和减少癫痫和小鼠癫痫的研究，并完善长期癫痫发作控制的实验。我们估计，在这个项目中，筛选40种化合物将需要100只动物，将这些药物开发过程中的动物使用量减少3900只。该项目极有可能有助于解开Epilim在人类人群中阻止癫痫的复杂方式，并开发治疗癫痫的新方法。

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.