PDE4D-NAMs for Treating Cognitive Impairment

用于治疗认知障碍的 PDE4D-NAM

• 批准号: 8910545
• 负责人: Mark E Gurney
• 金额: $ 9.69万
• 依托单位: TETRA DISCOVERY PARTNERS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8910545
• 关键词: Activities of Daily Living; Address; Adult; Affect; Aftercare; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Aricept; Binding; Biochemical; Biological Assay; Biological Availability; Biological Markers; Boxing; Brain; Brain Part; CREB1 gene; Central Nervous System Diseases; Cholinesterase Inhibitors; Clinical; Clinical Trials; Clinical dementia rating scale; Cocrystallography; Cognition; Cognitive; Collaborations; Cyclic AMP-Dependent Protein Kinases; Cytochrome P450; Dementia; Demographic Aging; Dendritic Spines; Deposition; Developed Countries; Diagnostic; Dimensions; Dose; Drug Targeting; Elderly; Enrollment; Functional disorder; Funding; Generations; Goals; Health; Hepatocyte; Hippocampus (Brain); Human; Impaired cognition; In Vitro; Individual; Knowledge; Lead; Life; Long-Term Potentiation; Measures; Medical; Memory; Mental Depression; Metabolic Activation; Metabolism; Modeling; Monkeys; Morphology; National Institute on Aging; Oral; Outcome; Paired-Associate Learning; Pathology; Pathway interactions; Patients; Peptides; Persons; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Plasma; Population; Prevention; Property; Publishing; Recommendation; Retrieval; Rodent; Rolipram; Sales; Senile Plaques; Short-Term Memory; Solubility; Structure; Sum; System; Testing; Therapeutic; Toxic effect; United States National Institutes of Health; Vomiting; base; cerebral atrophy; clinical research site; clinically significant; cognitive function; cooperative study; coping; design; drug market; experience; genotoxicity; impression; improved; in vivo; inhibitor/antagonist; instrument; member; mental state; mild cognitive impairment; mouse model; neurochemistry; neuroimaging; neuron loss; phosphodiesterase 4D; phosphoric diester hydrolase; pre-clinical; programs; scaffold; screening; synaptic function; working group

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is an increasing medical burden due to the aging demographics of the US population. The most common form of dementia among older adults, AD affects parts of the brain important for memory formation and retrieval, seriously impairing a person's ability to live independently and cope with daily activities. In collaboration with the NIH Blueprint Neurotherapeutics Program, we seek to develop phosphodiesterase Type 4 (PDE4) allosteric modulators for improving cognition in accordance with the Target Product Profile below. Ideally, the therapeutic will improve cognition in MCI patients and impact AD pathophysiology, thereby slowing conversion to probable AD. Drug PropertiesMinimum Acceptable ResultIdeal ResultPrimary Drug IndicationImprovement of cognition in persons with Mild Cognitive Impairment (MCI) due to probable ADSlowing of conversion from MCI to probable ADPatient PopulationPatients with MCI due to probable AD according to the NIAA/AA working group criteriaPatients with MCI due to probable AD according to the NIAA/AA working group criteriaDelivery ModeOralOralTreatment DurationChronicChronicRegimenOral, once dailyOral, once daily

描述（由申请人提供）：由于美国人口老龄化，阿尔茨海默氏病（AD）是一种日益增加的医疗负担。 AD 是老年人中最常见的痴呆症，它会影响大脑中对记忆形成和检索很重要的部分，严重损害一个人独立生活和应对日常活动的能力。我们与 NIH 蓝图神经治疗计划合作，寻求开发 4 型磷酸二酯酶 (PDE4) 变构调节剂，以根据下面的目标产品简介改善认知。理想情况下，该治疗将改善 MCI 患者的认知并影响 AD 病理生理学，从而减缓向可能 AD 的转化。 药物特性最低可接受结果理想结果主要药物适应症改善因可能的 AD 导致的轻度认知障碍 (MCI) 患者的认知能力减缓从 MCI 到可能的 AD 的转化患者人群根据 NIAA/AA 工作组标准，因可能的 AD 导致的 MCI 患者由于可能的 AD 导致的 MCI 患者AD按照NIAA/AA工作组标准交付模式口服口服治疗持续时间慢性慢性治疗方案口服，每日一次口服，每日一次