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

开发用于治疗神经退行性疾病的线粒体通透性转换孔抑制剂

• 批准号: 10017105
• 金额: $ 239.09万
• 依托单位: NRG THERAPEUTICS LTD
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10017105
• 关键词: Development; Mitochondrial; Permeability; Transition; Pore

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.

虽然随着公共卫生的重大进步和现代医学的发展，预期寿命稳步增长，但健康预期寿命的增长幅度并不相同。因此，英国的老龄化人口正面临着晚年长期健康不佳的危机，老年人经常发展一种或多种与年龄相关的慢性疾病，如关节炎，癌症，2型糖尿病，心血管和神经退行性疾病。帕金森病（PD）是英国第二大流行的神经退行性疾病，影响约145，000人。帕金森氏症患者会出现使人衰弱的运动（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治疗方法都只能控制症状，不能阻止或减缓疾病的进展。运动神经元疾病（MND）是一种罕见的致命性神经退行性疾病，影响大脑和脊髓中的神经细胞，导致对运动，说话，进食和呼吸所需的肌肉失去控制。这通常导致在诊断后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的（几个月）益处。NRG Therapeutics（NRG）是一家总部位于英国的创新型生物技术公司，拥有神经科学药物发现和线粒体生物学方面的专业知识，正在开发治疗慢性神经退行性疾病（如PD和MND）的新药。线粒体是细胞的发电站或电池，因此对维持细胞健康至关重要，但现在有大量证据表明，线粒体功能障碍或功能障碍在许多退行性疾病中很常见。NRG的研究性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。该项目将资助NRG的主要药物发现项目的进展，并产生临床前数据包，证明其候选药物渗透到大脑，保护线粒体，在动物模型中防止脑细胞死亡，并且在长期给药后安全且耐受性良好。