The biochemical stratification of amyotrophic lateral sclerosis

肌萎缩侧索硬化症的生化分层

• 批准号: MR/Y001095/1
• 负责人: David Lester
• 金额: $ 26.98万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY001095%2F1
• 关键词: biochemical; stratification; amyotrophic; lateral; sclerosis

Motor neuron disease (MND, also known as amyotrophic lateral sclerosis, ALS) is a fatal, incurable disease that causes progressive muscle weakness. MND affects people in very different ways: weakness can begin first in any body part, sometimes people have symptoms affecting their thoughts and behaviours as well as weakness, and, although people with MND live on average for less than three years after weakness develops, some will live for over a decade. Why MND behaves in these different ways is not understood, but it is likely that it relates to differences in the way that the disease affects cells in the nervous system. These differences are probably a major reason why a large number of drug trials for MND have failed.My research will study the molecules (called proteins) that perform virtually all of the tasks in every cell of the body, including nerve cells. I will examine the different patterns of proteins found in the spinal fluid, reflecting changes in nervous system cells, of a large number of MND patients to try to understand what is happening in the nervous system to account for the differences in the ways that MND affects people. Through an advanced computer technique called machine learning, I aim to identify protein patterns that relate to different patterns of MND. Using these protein patterns, I hope that in five years' time this will enable drug trials to be more specifically tailored to a person's MND, improving the likelihood of drug trial success.

运动神经元疾病（MND，也称为肌萎缩侧索硬化症，ALS）是一种致命的，无法治愈的疾病，导致进行性肌肉无力。MND以非常不同的方式影响人们：虚弱可以开始首先在身体的任何部位，有时人们会有影响他们的思想和行为以及虚弱的症状，虽然MND患者在虚弱发展后平均生活不到三年，但有些人会活十多年。为什么MND以这些不同的方式表现尚不清楚，但很可能与疾病影响神经系统细胞的方式不同有关。这些差异可能是大量针对MND的药物试验失败的主要原因。我的研究将研究在身体的每个细胞（包括神经细胞）中执行几乎所有任务的分子（称为蛋白质）。我将研究在大量MND患者的脊髓液中发现的不同蛋白质模式，反映神经系统细胞的变化，试图了解神经系统中发生了什么，以解释MND影响人们的方式的差异。通过一种称为机器学习的先进计算机技术，我的目标是识别与不同MND模式相关的蛋白质模式。利用这些蛋白质模式，我希望在五年的时间内，这将使药物试验能够更具体地针对一个人的MND，提高药物试验成功的可能性。