Alpha-GPC and Plasmalogen Nootropics

Alpha-GPC 和缩醛磷脂促智药

• 批准号: 522036-2017
• 负责人: Reaney, Martin
• 金额: $ 1.82万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=640757
• 关键词: Alpha; GPC; Plasmalogen; Nootropics

Med-Life discoveries (MLD) has developed plasmalogen restoration as a therapy for Alzheimer's disease that is based on a synthetic plasmalogen precursor composed of naturally occurring metabolites. The drug is converted by the body into a variety of plasmalogen lipid species required by neurons. Preclinical evaluation of MLD's plasmalogen restoration therapy is nearly complete, and synthesis is being scaled up to support an FDA IND submission and a Phase I clinical trial. Together with our collaborators, MLD is in the final stages of planning for trials in patients with mild cognitive impairment. Patients treated with plasmalogen precursors are able to release acetyl choline to the synaptic cleft with greater efficiency. Similarly the compound glycerylphosphorylcholine (GPC) is sold as nootropic for treatment of Alzheimer's disease based on its action as a parasympathomimetic precursor of acetylcholine. GPC also acts as a nutraceutical and clinical studies show its effects on cognitive performance in Alzheimer's patients. GPC affects lipid metabolic rates as it is a precursor to phosphatidyl choline. It is low toxicity and it is consumed at high concentrations (300 mg to 1,200 mg daily) in most studies. An ethanol plant like the one in Belle Plaine, Saskatchewan could produce about 1 billion 500 mg doses per year. Individuals are self treating Alzheimer's with GPC and they might consume this compound in conjunction with other clinical treatments such as plasmalogens. It would be valuable to first determine the GPC quality. In the future, once a pure source of GPC is identified an appropriate clinical trial can be devised. Current commercial GPC preparations arise from lipid hydrolysis but GPC from ethanol production is new. Our goal in this proposal is to determine commercial GPC purity and compare it to GPC from ethanol production. We have prepared GPC concentrates in the laboratory and will scale up GPC production from ethanol. In future research we will determine if alpha-GPC is safe to use in conjunction with plasmalogen. NSERC ENGAGE proposal will conclude with the production of ~200 g of GPC at the University of Saskatchewan's Bioprocessing Pilot Plant.

Med-Life Discovery(MLD)已经开发出血浆原修复作为阿尔茨海默病的治疗方法，这是基于一种由自然发生的代谢物组成的合成血浆蛋白原前体。这种药物被人体转化为神经元所需的各种血浆蛋白原脂质物种。MLD的纤溶酶原修复疗法的临床前评估接近完成，合成正在扩大规模，以支持FDA IND提交的文件和I期临床试验。与我们的合作者一起，MLD正在规划对轻度认知障碍患者的试验的最后阶段。接受纤溶酶原前体治疗的患者能够更有效地将乙酰胆碱释放到突触间隙。同样，基于其作为乙酰胆碱的副交感神经前体的作用，复合甘油基磷胆碱(GPC)被作为促性剂出售用于治疗阿尔茨海默病。GPC也是一种营养食品，临床研究表明它对阿尔茨海默病患者的认知表现有影响。GPC影响脂质代谢率，因为它是磷脂酰胆碱的前体。它的毒性很低，在大多数研究中都是在高浓度(每天300毫克到1200毫克)的情况下食用。像萨斯喀彻温省贝勒平原这样的乙醇工厂每年可以生产大约1500毫克的剂量。个人正在使用GPC自我治疗阿尔茨海默氏症，他们可能会与其他临床治疗方法(如血浆原)一起服用这种化合物。首先确定GPC质量是有价值的。在未来，一旦确定了GPC的纯来源，就可以设计出合适的临床试验。目前商品化的GPC制剂是由脂肪水解而来的，但从乙醇生产的GPC是新的。我们在这项提案中的目标是确定商业GPC的纯度，并将其与乙醇生产的GPC进行比较。我们已经在实验室中制备了GPC浓缩物，并将扩大从乙醇中生产GPC的规模。在未来的研究中，我们将确定α-GPC与血浆蛋白原联合使用是否安全。NSERC Engage提案的最后将是在萨斯喀彻温大学的生物处理试点厂生产~200克GPC。