Development of Mitochondrial Permeability Transition Pore Inhibitors for the Treatment of Neurodegenerative Diseases

虽然随着公共卫生的重大进步和现代医学的发展，预期寿命稳步增加，但健康的预期寿命并没有增加到同样的程度。因此，英国老龄化人口在晚年面临着长期健康不佳的危机，老年人往往会患上一种或多种与年龄相关的慢性病，如关节炎、癌症、2型糖尿病、心血管和神经退行性疾病。帕金森氏病(PD)是英国第二大最常见的神经退行性疾病，影响约14.5万人。帕金森氏症患者会出现运动性衰弱(震颤、僵硬、肌肉僵硬)和非运动性(痴呆症、抑郁症)症状。不幸的是，目前所有的帕金森病治疗方法都只能控制症状，并不能阻止或减缓疾病的发展。运动神经元病(MND)是一种罕见的致命神经退行性疾病，影响大脑和脊髓中的神经细胞，导致运动、说话、饮食和呼吸所需的肌肉失去控制。这通常会导致确诊后3-5年内死亡。只有一种治疗MND的方法显示出在减缓疾病进展方面(几个月内)有轻微的好处。因此，对于这两种疾病，都迫切需要能够治愈或阻止疾病进展的新药。NRG Treeutics(NRG)是一家总部位于英国的创新生物技术公司，在神经科学药物发现和线粒体生物学方面具有专长，该公司正在开发治疗PD和MND等慢性神经退行性疾病的新药。线粒体是细胞的动力源或电池，因此对维持细胞健康是必不可少的，但现在有大量证据表明，线粒体失效或功能障碍在许多退行性疾病中很常见。NRG正在研究的新药已被证明可以保护线粒体和防止脑细胞死亡，因此有可能阻止或显著减缓PD或MND患者的疾病进展。该项目将为NRG的领先药物发现项目的进展提供资金，并生成临床前数据包，证明其候选药物可以渗透到大脑中，保护线粒体，在动物模型中防止脑细胞死亡，并且在长期服药后是安全的和良好的耐受性。

Although life expectancy has increased steadily following major advances in public health and the development of modern medicines development, _healthy_ life expectancy has not increased to the same degree. Consequently, the UK's aging population is facing a crisis of extended periods of ill health in later life, with older adults often developing one or more age-related chronic disease such as arthritis, cancer, type 2 diabetes mellitus, cardiovascular and neurodegenerative disorders.Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in the UK, affecting ~145,000 individuals. People with Parkinson's experience debilitating motor (tremor, rigidity, muscle stiffness) and non-motor (dementia, depression) symptoms. Unfortunately, all current treatments for PD control symptoms only and do not halt or slow progression of disease. Motor neuron disease (MND), is a rare fatal neurodegenerative disorder that affects the nerve cells in the brain and the spinal cord resulting in a loss in control of the muscles needed to move, speak, eat, and breathe. This typically leads to death within 3-5 years of diagnosis. There is only one treatment for MND that has shown a modest (by a few months) benefit in slowing down progress of the disease. For both diseases, novel medicines that can cure or halt disease progression, are therefore desperately needed.NRG Therapeutics (NRG), an innovative UK-based biotech with expertise in neuroscience drug discovery and mitochondrial biology, is developing novel medicines for the treatment of chronic neurodegenerative diseases such as PD and MND. Mitochondria are the powerhouses or batteries of cells and therefore essential for maintaining cell health but there is now a substantial body of evidence showing that mitochondrial failure or dysfunction is common across many degenerative diseases. NRG's investigational new drugs have been shown to protect mitochondria and prevent the death of brain cells and therefore have the potential to halt or significantly slow the progression of disease in individuals with PD or MND.This project will fund progression of NRG's lead drug discovery project and generate a preclinical data package that demonstrates its drug candidates penetrate into the brain, protect mitochondria, prevent brain cell death in animal models and are safe & well tolerated following chronic dosing.