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

以 tau 蛋白为靶点开发新型阿尔茨海默病疗法

基本信息

批准号：
10010108
负责人：
Glenn Larsen
金额：
$ 147.6万
依托单位：
AQUINNAH PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10010108
关键词：
Alzheimer&apos s Disease Alzheimer&apos s disease brain Alzheimer&apos s disease model Alzheimer&apos s disease patient Alzheimer&apos s disease therapeutic Alzheimer&apos s disease therapy Animal Model Behavioral Biological Biological Assay Biology Boston Canis familiaris Cells Chemicals Chronic stress Clinic Complex Deposition Development Disease Disease Management Disease Progression Environment Functional disorder Genetic Polymorphism Grant Human Impaired cognition Industry Standard Laboratories Laboratory Research Lead Link Liquid substance Membrane Memory Loss Messenger RNA Molecular Target Mus Mutation Nerve Degeneration Neurodegenerative Disorders Neurofibrillary Tangles Neurons Oral Pathologic Pathology Pathway interactions Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Phase Process Proteins Rattus Role Sampling Senile Plaques Senile dementia Series Small Business Innovation Research Grant Societies Source Stress Structure Synapses Tauopathies Testing Toxicology Transgenes Translating Universities abeta accumulation advanced disease analog cerebral atrophy cholinergic neuron cognitive function design drug candidate drug development effective therapy efficacy testing high throughput screening improved in vivo inhibitor/antagonist knock-down lead optimization medication safety mouse model neuron loss new therapeutic target novel novel therapeutic intervention pharmacophore phase 1 study programs proteostasis response safety assessment safety study screening small molecule small molecule inhibitor stem stress granule stress reduction symptomatic improvement targeted treatment tau Proteins tau aggregation tau interaction therapeutic development

项目摘要

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.

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）动物模型和动物模型）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。