Alzheimers 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.
Public Health Relevance Statement: With our aging population, Alzheimers disease (AD) and related dementia (ADRD) are adversely impacting the healthy lifespan. We have developed a novel omega-3 fatty acid that specifically penetrates the brain and minimizes the memory loss in mice. Here, as a proof of concept, we will test this novel omega-3 fatty acid as a protective treatment for AD mouse models.
Project Terms: Address; age related; Age-associated memory impairment; Aging; aging population; Agreement; Alzheimer's Disease; Alzheimer's disease model; Alzheimer's disease related dementia; American; analytical method; Behavioral; Biochemical; Blood - brain barrier anatomy; Brain; Certification; Chemicals; Chicago; Clinical Trials; cognitive function; Collaborations; commercialization; Control Groups; Cyclic GMP; Data; Dementia; dementia risk; Development; dietary supplements; Docosahexaenoic Acids; Drug Delivery Systems; early onset; efficacy testing; Eicosapentaenoic Acid; Elderly; epidemiology study; Euphausiacea; experience; experimental study; Failure; Fish Oils; functional decline; Future; Genetic Models; Goals; Human; Illinois; improved; Industry; innovation; Lead; Licensing; Lipase; Longevity; Lysophospholipids; Marketing; Measures; Memory; Memory Loss; Metabolic; mouse model; Mus; Natural Products; novel; novel strategies; Oils; Omega-3 Fatty Acids; Outcome; Peripheral; Phase; phase 2 study; Population; prevent; Prevention; Preventive; Preventive measure; Preventive treatment; Process; process optimization; Production; Research; research and development; Series; Techniques; Testing; Tissues; treatment effect; Triglycerides; Universities
