A Novel DHA Treatment Approach for Alzheimer's Disease

治疗阿尔茨海默病的新 DHA 方法

• 批准号: 10082124
• 负责人: Brian Thomas Layden
• 金额: $ 34.96万
• 依托单位: OROCHEM TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10082124
• 关键词: Address; Age-associated memory impairment; Aging; Agreement; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease related dementia; American; Behavioral; Biochemical; Blood - brain barrier anatomy; Brain; Certification; Chemicals; Chicago; Clinical Trials; Collaborations; Control Groups; Cyclic GMP; Data; Dementia; Development; Docosahexaenoic Acids; Drug Delivery Systems; Eicosapentaenoic Acid; Elderly; Euphausiacea; Failure; Fish Oils; Future; Genetic Models; Goals; Human; Illinois; Industry; Lead; Licensing; Lipase; Longevity; Lysophospholipids; Marketing; Measures; Memory; Memory Loss; Metabolic; Mus; Natural Products; Oils; Omega-3 Fatty Acids; Outcome; Peripheral; Phase; Population; Prevention; Preventive; Preventive measure; Preventive treatment; Process; Production; Research; Series; Techniques; Testing; Tissues; Triglycerides; Universities; age related; aging population; analytical method; cognitive function; commercialization; dementia risk; dietary supplements; early onset; efficacy testing; epidemiology study; experience; experimental study; functional decline; improved; innovation; mouse model; novel; novel strategies; phase 2 study; prevent; process optimization; research and development; treatment effect

Alzheimer’s disease (AD) and related dementia (ADRD) are adversely impacting the healthy lifespan in our aging population. Fish oil has been suggested to improve AD/ADRD outcomes. The omega 3 fatty acids (Om3FA) in fish oil in particular DHA (docosahexaenoic acid) is a key molecule. Some data exists that DHA is beneficial for protection against age related cognitive decline and related dementia such as AD. However, current dietary supplements of Om3FA do not appreciably increase DHA levels in the brain. Our data explains why multiple human clinical trials failed with DHA treatment for preventing and/or treating AD/ADRD. We have discovered that this failure to cross the blood-brain barrier is because the Om3FA from these supplements are absorbed in the form of triacylglycerols, whereas the specific transporter (called Mfsd2a) at the blood brain barrier requires a lysophospholipid (LPC) form of DHA. Because of this, when we treat with lipase, it results in the LPC form of DHA. Then, when we treat mice with this form, mice have a substantial enrichment of the brain DHA, as compared to control group and a notable memory benefit. Thus, the goal of this phase 1 is to test if LPC-DHA effects memory in AD mouse models. We will specifically explore the behavioral and biochemical effects of this treatment approach. Through collaboration with the University of Illinois at Chicago, with expertise in Om3FA and mouse models, and our expertise in chemical separation and Om3FA isolation techniques, we are poised to test the efficacy of this novel treatment. Moreover, we are prepared for Phase 2 studies, which will focus on development of pilot scale production/isolation processes of this modified DHA. This will eventually lead to marketing and commercialization to protect and/or prevent against AD development in Phase 3.

阿尔茨海默氏病（AD）和相关痴呆症（ADRD）正在对健康产生不利影响 我们老化的人口中的寿命。建议鱼油改善AD/ADRD结果。 尤其是鱼油中的Omega 3脂肪酸（OM3FA）（docosahexaenoic acid）是关键 分子。有些数据存在DHA有益于保护与年龄相关的认知 衰落和相关痴呆症，例如AD。但是，OM3FA的当前饮食补充 没有理解的是大脑中的DHA水平。我们的数据解释了为什么多个人类临床 通过DHA治疗方法预防和/或治疗AD/ADRD的试验失败。我们发现了 这种未能越过血脑屏障的是因为这些补充剂的OM3FA 以三酰基甘油的形式吸收，而特定的转运蛋白（称为MFSD2A） 血脑屏障需要DHA的溶血磷脂（LPC）形式。因此，当我们 用脂肪酶处理，导致DHA的LPC形式。然后，当我们用这种形式治疗小鼠时， 与对照组相比，具有大脑DHA的大量酶 记忆益处。这阶段1的目的是测试LPC-DHA是否影响AD鼠标的内存 型号。我们将特别探讨该处理的行为和生化效应 方法。通过与芝加哥伊利诺伊大学合作，拥有专业知识 OM3FA和鼠标模型，以及我们在化学分离方面的专业知识和OM3FA隔离 技术，我们被中毒以测试这种新型治疗的效率。而且，我们已经做好了 对于第二阶段研究，该研究将重点介绍该试验量表生产/隔离过程的发展 修改的DHA。这最终将导致营销和商业化，以保护和/或阻止 反对第3阶段的AD开发。