Development of S-PCT3010 to treat cognitive impairment in Alzheimers Disease
开发S-PCT3010治疗阿尔茨海默病认知障碍
基本信息
- 批准号:10287800
- 负责人:
- 金额:$ 45.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-01 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:AgeAge-MonthsAgonistAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease patientAmericanAmyloid Beta A4 Precursor ProteinAnimalsArrestinsBehavioralBiochemicalBiological AvailabilityBrainBrain regionCause of DeathCognition DisordersCognitiveCompulsive BehaviorCorpus striatum structureDataDementiaDevelopmentDiseaseDopamineEtiologyFinancial HardshipGTP-Binding ProteinsGoalsHippocampus (Brain)Impaired cognitionImpulsive BehaviorIn VitroL-DOPA induced dyskinesiaLinkMeasurementMediatingMemoryMemory DisordersMemory LossModelingMusMutationNeurodegenerative DisordersNeurofibrillary TanglesNorepinephrineOralParkinson DiseasePathologicPathologyPathway interactionsPatientsPerformancePharmaceutical PreparationsPharmacologic SubstancePharmacologyPhasePilot ProjectsPrefrontal CortexPropertyPublishingRattusResearch ContractsResearch PersonnelRodentRodent ModelSenile PlaquesSignal PathwaySignal TransductionSliceSmall Business Innovation Research GrantTestingTherapeuticTherapeutic UsesTrainingTransgenic MiceUnited StatesUniversitiesVendorabeta accumulationbasebehavioral studybeta-arrestinblood-brain barrier penetrationcognitive functioncognitive impairment in Parkinson&aposscognitive taskcostdensityflexibilityhuman old age (65+)improvedin vivoinhibitor/antagonistmortality riskmotor impairmentmouse modelneurotransmissionnonhuman primatenoradrenaline transporternovelpresenilin-1recruitspatial memorysustained attention
项目摘要
PolyCore Therapeutics LLC is developing S-PCT3010 as a therapeutic for improved cognitive
function in patients suffering from Parkinson’s Disease and is proposing to evaluate S-PCT3010
as a therapeutic for improved cognitive function in Alzheimer’s patients. S-PCT3010 is a
selective D3R agonist with biased signaling through the G-protein pathway which does not
recruit -arrestin. The drug does not induce tolerance in vitro or in vivo in rats. Further, S-
PCT3010 is a selective inhibitor of norepinephrine transporter and promotes improvement in
sustaining attention and cognitive flexibility in rodent models of Parkinson’s Disease without
producing compulsive or impulsive behaviors. S-PCT3010 is highly pharmaceutically tractable
with excellent oral bioavailability and blood brain barrier penetration. In this proposal, PolyCore
Therapeutics LLC is proposing to complete pilot studies in a in vivo transgenic mouse model of
Alzheimer’s Disease evaluating both behavioral and pathological changes following S-PCT3010
administration.
Per the Alzheimer’s Association, an estimated 5.8 million Americans age 65 and older
are living with Alzheimer's dementia in 2020 with eighty percent over 75 years old. These
numbers represent one in ten people over the age of 65 living with various cognitive
impairments. Alzheimer's Disease also represents a significant risk of death and is the sixth-
leading cause of death in the United States. The financial burden of Alzheimer's Disease is
projected to cost more than $1.1 trillion dollars in 2020, and a significant portion of this cost
relates to patient management around cognitive disorders and dementia. In this application,
PolyCore Therapeutics LLC teams with leading Parkinson’s and Alzheimer’s researchers at
Drexel University to evaluate the changes in cognitive function resulting from Alzheimer’s
Disease. The team plans to evaluate S-PCT3010 for use in mitigation of cognitive disorders
and memory loss using a transgenic mouse model of Alzheimer’s disease. PolyCore
Therapeutics LLC is actively developing S-PCT3010 for Parkinson Disease under an ongoing
Phase II SBIR (1R44NS117201-01).
PolyCore Therapeutics LLC 正在开发 S-PCT3010 作为改善认知的治疗方法
帕金森病患者的功能,并提议评估 S-PCT3010
作为改善阿尔茨海默病患者认知功能的治疗方法。 S-PCT3010是一种
选择性 D3R 激动剂,通过 G 蛋白途径产生偏向信号传导,但不
招募-arrestin。该药物在体外或体内不会诱导大鼠耐受。此外,S-
PCT3010 是去甲肾上腺素转运蛋白的选择性抑制剂,可促进改善
在帕金森病啮齿动物模型中保持注意力和认知灵活性,而无需
产生强迫或冲动的行为。 S-PCT3010 具有高度的药物易处理性
具有优异的口服生物利用度和血脑屏障渗透性。在本提案中,PolyCore
Therapeutics LLC 提议完成体内转基因小鼠模型的初步研究
评估 S-PCT3010 后的行为和病理变化的阿尔茨海默病
行政。
根据阿尔茨海默病协会的数据,估计有 580 万美国人年龄在 65 岁及以上
到 2020 年,将患有阿尔茨海默氏痴呆症,其中 80% 的人年龄超过 75 岁。这些
这个数字代表十分之一的 65 岁以上的人患有各种认知障碍
损伤。阿尔茨海默氏病也是一种重大的死亡风险,是第六大疾病
美国的首要死因。阿尔茨海默病的经济负担是
预计到 2020 年将花费超过 1.1 万亿美元,其中很大一部分
涉及认知障碍和痴呆症的患者管理。在这个应用程序中,
PolyCore Therapeutics LLC 与领先的帕金森氏症和阿尔茨海默氏症研究人员合作
德雷塞尔大学评估阿尔茨海默氏症引起的认知功能变化
疾病。该团队计划评估 S-PCT3010 在缓解认知障碍方面的用途
和记忆丧失使用阿尔茨海默病转基因小鼠模型。多核
Therapeutics LLC 正在积极开发用于治疗帕金森病的 S-PCT3010
II 期 SBIR (1R44NS117201-01)。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
G-protein biased signaling agonists of Dopamine D3 receptor promote distinct activation patterns of ERK1/2.
多巴胺 D3 受体的 G 蛋白偏向信号激动剂促进 ERK1/2 的不同激活模式。
- DOI:10.1016/j.phrs.2022.106223
- 发表时间:2022
- 期刊:
- 影响因子:9.3
- 作者:Xu,Wei;Bearoff,Frank;Kortagere,Sandhya
- 通讯作者:Kortagere,Sandhya
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