Long-term toxicology studies for Posiphen; 6 month in rats and 9 months in dogs

Posiphen 的长期毒理学研究；

• 批准号: 10018610
• 负责人: Maria Maccecchini
• 金额: $ 97.54万
• 依托单位: ANNOVIS BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10018610
• 关键词: Age; Alzheimer' s Disease; Alzheimer' s disease model; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Animals; Applications Grants; Axonal Transport; Behavior monitoring; Blood - brain barrier anatomy; Brain; Canis familiaris; Cerebrospinal Fluid; Clinical; Clinical Pathology; Clinical Research; Cognitive; Data; Disease; Dose; Drug Kinetics; Drug Targeting; Drug usage; Formulation; Gelatin; Human; Impairment; Incidence; Inflammation; Inflammatory; Kinetics; Laboratories; Lead; Learning; Length; Memory; Molecular Weight; Mus; Nerve Degeneration; Neurons; Neurotransmitters; Oral; Organ; Parkinson Disease; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Preparation; Property; Proteins; Quality of life; Rattus; Recovery; Reporting; Research; Rivers; Safety; Stable Isotope Labeling; Tartrates; Testing; Therapeutic; Toxic effect; Toxicokinetics; Toxicology; Transgenic Mice; Translations; Traumatic Brain Injury; aging population; albino rat; alpha synuclein; capsule; cell motility; efficacy study; improved; inhibitor/antagonist; mild cognitive impairment; mouse model; neuron loss; neurotoxic; neurotrophic factor; novel; pre-clinical; preservation; prevent; release factor; safety study; sex; small molecule; tau Proteins

PAR 18-820 Summary Long term toxicology studies for Posiphen®; 6 months in rats and 9 months in dogs Posiphen tartrate is a small molecule of 487.5 molecular weight, with a Log P of 2.22 resulting oral availability and high blood-brain barrier penetrability. It is a translational inhibitor of neurotoxic proteins, APP, tau and α-synuclein. By inhibiting these proteins, posiphen normalizes axonal transport, lowers inflammation and protects nerve cells from dying. This novel mechanism promises stop or slow the course of neurodegeneration and to give people with cognitive difficulties the possibility of living a healthy and independent live way into old age. In order to study this drug in Alzheimer’s and/or Parkinson’s patients we need long term tox studies in animals. We propose to conduct two animal toxicology studies: a 6 month rat study with 1 month recovery and a 9 month dog study with 1 month recovery. During the study the animals will be monitored for behavior and safety and after the study the organs and the brain will be evaluated for toxicological findings. We have already progressed posiphen through 3 human phase I safety studies and ADCS started a pharmacodynamic SILK phase IIa study in mild to moderate AD patients in summer of 2016. The data from the phase IIa together with the data from the proposed animal tox studies will allow us to enter posiphen into a 2 to 3 year pivotal phase II/III study in AD patients to show efficacy. The Alzheimer’s field has been dominated by approaches that prevent the processing to Aβ or remove Aβ in one of its many forms. Posiphen prevents the synthesis of APP and hence of Aβ. Accordingly the Parkinson’s field uses similar approaches to inhibit levels of α-synuclein or LRRK. Again posiphen prevents the synthesis of α-synuclein. By normalizing the levels APP/Aβ, tau/phopho-tau and α- synuclein posiphen prevents the formation of toxic products and prevents death of nerve cells. 1

第18-820杆 概括 POSIPHER®的长期毒理学研究；老鼠6个月，狗9个月 posifen tartrate是487.5分子量的小分子，log P为2.22，由2.22产生口服 可用性和高脑屏障的渗透性。它是一种翻译的神经毒性蛋白抑制剂， 应用，tau和α-突触核蛋白。通过抑制这些蛋白质，Posiphen使轴突运输归一化，降低 炎症并保护神经细胞免于死亡。这种新颖的机制承诺停止或减慢 神经退行性的过程，使认知困难的人生活的可能性 健康独立的现场直播方式。 为了在阿尔茨海默氏症和/或帕金森患者中研究这种药物 动物。我们建议进行两项动物毒理学研究：一项为期6个月的大鼠研究，有1个月 恢复和9个月的狗学习，康复1个月。在研究期间，动物将是 监控行为和安全性，在研究之后，将评估器官和大脑 毒理学发现。 我们已经通过3阶段的I阶段安全研究进步了Posiphen，ADC开始了 2016年夏季，在轻度至中度AD患者中的药物学丝IIA研究。 IIA阶段的数据以及拟议的动物托克斯研究的数据将使我们能够 在AD患者中以2至3年的II/III研究中输入POSIPHEN，以显示效率。 阿尔茨海默氏症的领域已由防止加工到Aβ或去除的方法主导 Aβ以其多种形式之一。 POSIPHEN防止APP的合成和Aβ的合成。根据 帕金森的领域采用类似的方法来抑制α-突触核蛋白或LRRK的水平。再次是波西普 防止α-突触核蛋白的合成。通过标准化水平APP/Aβ，Tau/Phopho-Tau和α- 综合蛋白POSIPHEN可防止有毒产物的形成并防止神经细胞的死亡。 1