A Novel DHA Treatment Approach for Alzheimer's Disease

阿尔茨海默病(AD)和相关痴呆症(ADRD)正在对健康造成不利影响 在我们老龄化的人口中的寿命。有人建议用鱼油来改善AD/ADRD的结果。 鱼油中的欧米伽3脂肪酸(Om3FA)，特别是DHA(二十二碳六烯酸)是关键 分子。已有数据表明，DHA有益于防止年龄相关的认知障碍 衰退和相关的痴呆，如阿尔茨海默病。然而，目前Om3FA的膳食补充剂做到了 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 预防和/或治疗AD/ADRD的DHA治疗试验失败。我们发现 这种未能通过血脑屏障的原因是这些补充剂中的Om3FA 以三酰甘油的形式被吸收，而特定的转运蛋白(称为Mfsd2a)在 血脑屏障需要溶血磷脂(LPC)形式的DHA。正因如此，当我们 用脂肪酶处理，它会导致DHA的LPC形式。然后，当我们用这种形式治疗老鼠时，老鼠 与对照组相比，脑内DHA有实质性的丰富和显著的 记忆方面的好处。因此，这一阶段的目标是测试LPC-DHA是否影响AD小鼠的记忆 模特们。我们将专门探讨这种治疗的行为和生化影响。 接近。通过与芝加哥伊利诺伊大学的合作，拥有 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，我们已经做好了准备 对于第二阶段研究，将重点开发该产品的中试规模生产/分离工艺 改性DHA。这最终将导致市场营销和商业化，以保护和/或防止 反对第三阶段的AD开发。

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.