A Novel DHA Treatment Approach for Alzheimer's Disease

阿尔茨海默病（AD）和相关痴呆（ADRD）对健康人有不利影响， 在我们老龄化的人口中。鱼油已被建议改善AD/ADRD结果。 鱼油中的欧米茄3脂肪酸（Om3FA），特别是DHA（二十二碳六烯酸）是一种关键的 分子。一些数据表明，DHA有助于防止与年龄相关的认知障碍。 衰退和相关的痴呆症，如AD。然而，目前Om3FA的膳食补充剂 不会明显增加大脑中的DHA水平。我们的数据解释了为什么多个人类临床 DHA治疗预防和/或治疗AD/ADRD试验失败。我们已经发现 这种无法穿过血脑屏障的现象是因为这些补充剂中的Om3FA 以三酰甘油的形式被吸收，而特定的转运蛋白（称为Mfsd2a）， 血脑屏障需要溶血磷脂（LPC）形式的DHA。因此，当我们 用脂肪酶处理，它导致LPC形式的DHA。然后，当我们用这种形式治疗小鼠时，小鼠 与对照组相比， 记忆的好处因此，该阶段1的目标是测试LPC-DHA是否影响AD小鼠的记忆 模型我们将特别探讨这种治疗的行为和生化影响 approach.通过与伊利诺伊大学芝加哥分校合作， Om3FA和小鼠模型，以及我们在化学分离和Om3FA分离方面的专业知识 技术，我们准备测试这种新疗法的疗效。此外，我们准备 第2阶段研究，重点是开发中试规模的生产/分离工艺， 改性DHA这将最终导致市场营销和商业化，以保护和/或防止 在第三阶段对抗AD的发展。

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.