Development of S-PCT3010 to treat cognitive impairment in Alzheimers Disease

PolyCore Therapeutics LLC正在开发S-PCT 3010作为改善认知功能的治疗药物 在帕金森病患者中的功能，并建议评估S-PCT 3010 作为改善阿尔茨海默病患者认知功能的治疗方法。S-PCT 3010是一种 选择性D3 R激动剂，具有通过G蛋白途径的偏向信号传导， 招募了一个叫arrestin的人。该药物在体外或大鼠体内均不诱导耐受性。此外，S- PCT 3010是去甲肾上腺素转运蛋白的选择性抑制剂， 维持注意力和认知灵活性在帕金森病的啮齿动物模型中， 产生强迫或冲动行为。S-PCT 3010是高度药学易处理的 具有优异的口服生物利用度和血脑屏障渗透性。在这份提案中，PolyCore Therapeutics LLC建议在体内转基因小鼠模型中完成初步研究， 阿尔茨海默病评估S-PCT 3010后的行为和病理变化 局 根据阿尔茨海默氏症协会的统计，估计有580万65岁及以上的美国人 到2020年，80%的老年痴呆症患者超过75岁。这些 这些数字代表了65岁以上的人中有十分之一的人患有各种认知障碍， 损伤阿尔茨海默病也是一种重大的死亡风险，是第六大- 美国的主要死因。老年痴呆症的经济负担是 预计到2020年将花费超过1.1万亿美元，其中很大一部分成本 与认知障碍和痴呆症的患者管理有关。在本申请中， 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， 德雷克塞尔大学评估阿尔茨海默氏症导致的认知功能变化 疾病该团队计划评估S-PCT 3010用于缓解认知障碍 和记忆丧失的研究。PolyCore Therapeutics LLC正在积极开发用于帕金森病的S-PCT 3010， 阶段II SBIR（1 R44 NS 117201 -01）。

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).