Targeting tau for the development of novel Alzheimer's disease therapeutics

项目摘要 阿尔茨海默病是一种神经退行性疾病，其特征是认知功能进行性下降， 功能和相应的β-淀粉样蛋白斑块和神经纤维缠结的积累，这两个标志 病理学目前可用于AD患者的药物通过改善神经元功能来控制疾病症状。 活性，但随着疾病的进展，疗效降低。在tau蛋白病如AD中，tau蛋白的积累 与神经元丧失和认知功能下降密切相关。AD药物靶向治疗的新方法 阿奎纳制药公司提出的发展源于本·沃洛津博士的发现， （波士顿大学和Aquinnah的联合创始人）和他的实验室，其中tau病理学（在AD大脑和大脑中） 动物模型中的应激颗粒（SG）。阿奎纳正在推进这些引人注目的 这些发现进一步开发了抑制tau-SGs形成的新型分子， 在SBIR I期确定的AD治疗。SBIR第二阶段应用的总体目标是 执行药物化学命中铅和铅优化计划，以推进我们的新化合物 用于治疗AD。

PROJECT SUMMARY Alzheimer’s Disease is a neurodegenerative disease characterized by a progressive decline in cognitive function and a corresponding accumulation of β-amyloid plaques and neurofibrillary tangles, the two hallmark pathologies. Drugs currently available to AD patients manage the disease symptoms by improving neuronal activity, but efficacy diminishes as the disease advances. In tauopathies such as AD, the accumulation of tau correlates closely with neuronal loss and decline of cognitive function. The novel targeted approach to AD drug development proposed by Aquinnah Pharmaceuticals stems from discoveries made by Dr. Ben Wolozin (Boston University and co-founder of Aquinnah) and his laboratory, in which tau pathology (in both AD brain samples and animal models) was observed in stress granules (SG). Aquinnah is advancing these compelling findings to further the development of novel molecules that inhibit the formation of tau-SGs as a novel treatment for AD that were identified in SBIR Phase I. The overall objective of this SBIR Phase II application is to perform a medicinal chemistry hit-to-lead and lead optimization program to advance our novel compounds for the treatment of AD.