Biomarkers in motor neuron disease - a longitudinal translational neuroimaging and CSF study

运动神经元病（MND）是一种毁灭性的神经退行性疾病，影响了英国约5000人。运动神经元的丧失会导致肌肉萎缩，影响四肢、吞咽，最终影响呼吸。从症状开始的平均生存期为3-4年。MND没有专门的检测方法，诊断主要依靠临床检查。许多患者从症状开始等待一年多才能得到确切的诊断。超过75种药物在临床试验中失败，但要确定缺乏疗效可能需要数月时间。这项研究将每六个月对一组MND患者进行一次脑磁共振成像（MRI），并结合周围脑脊液（CSF）的分子分析。牛津脑功能核磁共振中心（FMRIB）已经开发出了对大脑神经通路损伤高度敏感的技术，并且有当地的专业知识来研究脑脊液中与这些变化相关的分子。结合起来，预计这将提供疾病活动的标记，以改善诊断过程和临床药物试验的监测方式，因此无效的药物可以更快地打折。对疾病机制的新认识可能提供新的药物靶点。

Motor Neuron Disease (MND) is a devastating neurodegenerative condition affecting around 5000 people in the UK. Loss of motor neurons produces muscle wasting variably affecting the limbs, swallowing, and ultimately breathing. The average survival from symptom onset is 3-4 years. There is no specific test for MND and diagnosis relies mainly on clinical examination. Many patients wait more than a year from symptom onset to receive a firm diagnosis. Over 75 drugs have failed in clinical trials but it can take many months to establish lack of efficacy with certainty. This research will study a group of MND patients every six months using magnetic resonance imaging (MRI) of the brain in combination with molecular analysis of the surrounding cerebrospinal fluid (CSF). The Oxford Centre for Functional MRI Brain (FMRIB) has developed techniques highly sensitive to damage within nerve pathways in the brain, and there is local expertise to study the CSF for molecules associated with these changes. In combination it is expected this will provide markers of disease activity to improve the diagnostic process and the way clinical drug trials are monitored, so ineffective drugs can be more quickly discounted. New insights into disease mechanisms may provide novel drug targets.