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药的发展，预期寿命稳步增加，但健康预期寿命并没有增加到同样的程度。因此，英国的老龄化人口正面临着晚年长期不健康的危机，老年人经常患上一种或多种与年龄有关的慢性疾病，如关节炎、癌症、2型糖尿病、心血管和神经退行性疾病。帕金森氏症（PD）是英国第二大常见的神经退行性疾病，约有145,000人受到影响。帕金森氏症患者会经历衰弱的运动（震颤、僵硬、肌肉僵硬）和非运动（痴呆、抑郁）症状。不幸的是，目前所有的PD治疗方法只能控制症状，不能阻止或减缓疾病的进展。运动神经元病（MND）是一种罕见的致死性神经退行性疾病，它影响大脑和脊髓中的神经细胞，导致对运动、说话、进食和呼吸所需肌肉的控制丧失。这通常导致确诊后3-5年内死亡。只有一种治疗MND的方法在减缓疾病进展方面显示出适度（几个月）的益处。因此，对于这两种疾病，迫切需要能够治愈或阻止疾病进展的新药。NRG Therapeutics （NRG）是一家创新的英国生物技术公司，在神经科学药物发现和线粒体生物学方面具有专业知识，正在开发用于治疗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室或电池，因此对维持细胞健康至关重要，但现在有大量证据表明，线粒体衰竭或功能障碍在许多退行性疾病中很常见。NRG的研究新药已被证明可以保护线粒体并防止脑细胞死亡，因此有可能阻止或显著减缓PD或MND患者的疾病进展。该项目将资助NRG的先导药物发现项目的进展，并生成临床前数据包，证明其候选药物可以穿透大脑，保护线粒体，防止动物模型中的脑细胞死亡，并且在长期给药后是安全且耐受性良好的。

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.