Patents

Mechanistic Medicine

Maintaining the Physiology of Brain Aging by Modulation of the checks and balances of the multiple signaling pathways needed to prevent the age related changes associated with cognitive decline and Alzheimer’s Disease.

The physiology of brain aging in women and men is associated with molecular and cellular changes which if unrecognized results in impaired cognition, memory and executive function. Mechanistic medicine links the molecular cascade of healthy and unhealthy aging with the established and synergistic pharmacodynamic , pharmacokinetic activity of the four ingredients in CogniFemme, CogniHomme and more recently, CogniTrans. The following benefits are anticipated: maintenance of neuronal mass (cognitive reserve); neuronal health ( prevention of beta amyloid and phosphorylated tau protein; inflammatory cytokine and oxidative stress accumulation) ; neuronal energy ( increase in mitochondrial activity; normal blood brain barrier ,insulin sensitivity and glucose transport) ; neuronal function ( homeostasis between chemical messenger acetylcholine and it’s inhibitor acetylcholinesterase).

Measurement : Efficacy Monitoring Blood Biomarkers

Based on recent research ,Ab42,p-tau217,and the p-tau/ab42 ratio measured in blood correlates strongly with the key pathologies of Alzheimer’s disease : amyloid plaques and neurofibrillary  tangles . The correlation varies by disease stage ,with some markers reflecting early amyloid changes and others signaling tau accumulation. Missing are surrogate biomarkers that measure the individuals response to preventive interventions indicative of brain health and cognitive reserve, to encourage both long term compliance in otherwise asymptomatic subjects or to  adjust dosages if needed to ensure effective brain health protection.

Hence the proposed CogniAchE  blood biomarker based on existing assays for acetylcholinesterase. (AChE) This enzyme acts as a protein and has a reciprocal feedback relationship to beta amyloid, tau protein and brain inflammatory cytokines. The  latter three molecules  can increase AChE expression and vice versa. This may lead to the pathologies of amyloid , tau and proinflammatory cytokines. Thus CogniAChE is proposed as a surrogate measure of this process and is recommended as a 6 monthly blood test.

Cognitive Reserve (CR) and CogniBDNF/AChE

CR is a physiologic protective mechanism that provides neural networks that can delay the onset of age related cognitive decline due to the accumulation of amyloid and tau protein plaques .A high CR thus represents a slower rate of cognitive decline and is dependent upon the physiologic balance between brain stem cell maturation into functional neurons ( neurogenesis) and the natural death of old brain cells (apoptosis) . BDNF ( brain derived neurotrophic factor) is one  neurotrophic factor responsible  responsible for neurogenesis. Its age related decline when combined with an increase in AChE creates  an environment associated with memory and overall cognitive health. The BDNF/AChE ratio will quantify this change and is recommended every 6 months.

Cortisol Brain Health and CogniCort/DHEA

Cortisol – which increases with age – is neurotoxic. DHEA – it’s natural inhibitor, decreases with age. This age related  change is reflected in a higher cortisol/DHEA ratio and  serves as another  key biomarker that can be measured by existing saliva or blood assays .When combined with the above two tests  it will serve as additional markers for the efficacy of CogniFemme, CogniHomme and CogniTrans. 

CongniTrans (2004) : DHEA  vs 7 Keto  DHEA

DHEA  is a crucial neurosteroid also synthesized in the brain that support brain health by enhancing neurogenesis and by increasing synaptic plasticity improves memory.. This is a direct action, increasing Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) and by counteracting the negative effects of cortisol. DHEA is also metabolized in the brain to estrogen and testosterone. 7 keto -DHEA in a dose of 200mg/day is not converted to either sex steroids and has been shown to enhance memory without the androgenic or estrogenic effects associated with DHEA. CT has the same additional  ingredients as CogniHomme and  is proposed for use by transgender individuals.

Product Formulation: Micro Encapsulation and Functional Excipients

Multi -ingredient brain health promotion – to address the multiple factors associated with  brain aging – involves combining various  bioactive compounds to achieve synergistic effects that single ingredient supplements may not provide. This process is further enhanced by time and sustained release technologies, which manage how these ingredients are absorbed over time  to maintain steady therapeutic levels. All three proposed products  are formulated by micro encapsulation designed to achieve desired therapeutic brain health protection.

GLP-1 receptors agonists are showing significant potential to enhancing brain health by improving  vascular function and by stimulating  insulin sensitivity ,brain energy. Sucramalt (R) has been shown to increase a greater  GLP-1 release than standard sucrose due it’s  enhanced delayed carbohydrate absorption and has been included both as a sweetener and as a synergistic pharmacologically active  ingredient. in all three OCE’s.

A detailed description of the above can be found in both the CogniFemme (2013) and CogniHomme (2014) patents.

Summary Documentation