Alzheimer’s: The Next Chapter

Industry failed to cure Alzheimer’s. But by shifting focus to neuron restoration rather than removal of β-Amyloid and tau, an expensive industry strategy that has had little marginal effect, perhaps we can finally put an end to neurodegeneration.

Twitter: @Mike_Kisselgof | Telegram: @IamKrychek

As my father suffered from Parkinson’s and both babushka’s from Alzheimer’s/dementia, the quest to prevent neurodegeneration is that much more pertinent. The probability I suffer from either neurodegenerative disease is comparatively higher, unfortunately. And perhaps a selfish/arrogant motivation to pursue a cure. Nonetheless, it has become increasingly clear through my research and collaboration with Mitch Kling MD (Harvard Medical School, NIH Fellow) and Dayan Goodenowe PHD (Prodrome Sciences) in the IKU NeuroDRO that industry has failed in its pursuit to find a cure. On the other hand, it has done a miraculous job in creating new technologies identifying associated symptoms by primarily focusing on biomarkers β-Amyloid and tau…

My work with IKU has led me to discover a potential solution that will be offered as a supplement to first comers to the NeuroDRO. Rather than focusing on the removal of associated symptoms, which has done little to nothing in preventing neurodegeneration, increasing evidence supported by Upenn, ALZ Asoociation, and the NIH has shown that neuron restoration in the cell membrane, specifically the plasmalogen phospholipid, may be the answer. Our next step is to prove human efficacy of synthesized plasmalogen.

If effective, it would be addressing neurodegenerative disease longitudinally i.e. Alzheimer’s, Parkinson, and Huntington’s.

Let me explain :)

A Confused Biomarker

Why has industry failed in its quest to cure Alzheimer’s Disease? Well, it’s not due to unsurpassable technological challenges. That’s for sure. But rather to a failure in recognizing and targeting the underlying causative mechanisms of neurodegeneration. Industry misinterpreted a neuropathological symptom of neurodegeneration (β-Amyloid) as the actual cause of neurodegeneration. And targeting of β-Amyloid has been incredibly successful. In fact, we have very powerful imaging technology that can measure β-Amyloid in the brain. We have antibodies that can remove β-Amyloid from the brain. We have beta-secretase and gamma-secretase enzyme inhibitors that can block the formation of β-Amyloid the brain…

Yes, β-Amyloid is a powerful biomarker. It indicates that something is wrong in the brain. Just like black smoke coming out of your automobile exhaust pipe is a biomarker that indicates that something is wrong in the engine. But industry failed by misinterpreting a biomarker as being literally causal when the neural pathological and behavioral information strongly suggested otherwise. The confusion between a biomarker of causation and a biomarker as causation is much more common than it should be. β-Amyloid is a sensitive biomarker of abnormal neuron membrane structure and function. In order for β-Amyloid to accumulate in the brain, it means that the natural balance between the alpha-secretase and beta-secretase enzymes has been disrupted resulting in more amyloid precursor protein being processed by beta-secretase than normal and/or less of that protein is being processed by alpha-secretase.

The other challenge with the β-Amyloid hypothesis is that it is premised on the hypothesis that β-Amyloid is a neurotoxin and that it directly causes neurodegeneration. But the animal studies that support this hypothesis require very large amounts of amyloid and a long time to create toxicity. β-Amyloid in the brain is certainly not a good thing, however, the data that it is a toxic agent is lacking. To the contrary, there are many human neuropathological examples where you have very healthy brain function with massive loads of amyloid.

Restoration Rather than Removal

Other research suggests that rather than removing a weakly hypothesized neurotoxin that has repeatedly failed to produce a clinical benefit, restoring the natural balance in the membrane can potentially prevent the onset of neurodegeneration. The plasmalogen hypothesis targets neurodegeneration by addressing the core structural integrity of neurons that declines with age and disease — their membranes. Neuronal membrane dysfunction is a well documented mechanism that is associated with both β-Amyloid accumulation and clinical measurements such as cognition. A strong and growing body of evidence indicates that decreased blood and brain levels of a critical type of lipid called plasmalogens is the root cause of neurodegeneration.

What is a Plasmalogen?

It is a lipid that your brain requires for normal functioning. It is found in the neuron membrane where it facilitates healthy enzyme function and the membrane fusion and release of neurotransmitters.

Dr. Dayan Goodenowe explains plasmalogen

Evidence indicates low levels of plasmalogens is a key causative factor in neurodegeneration and that plasmalogen supplementation can prevent neurodegeneration. With no effective food supply of these lipids, the only way to elevate plasmalogen levels to protective levels is via supplementation.

Proposed Clinical Trials

Two institutions plan on conducting clinical trials to test human efficacy of plasmalogen supplementation on neurodegenerative disease. One of them being the University of Pennsylvania where Mitch Kling, MD will be leading an Alzheimer’s Association-funded plasmalogen supplementation trial in Alzheimer’s patients. The other being Prodrome Science who just opened their Prodrome Health facility in Saskatchewan, Canada where CEO Dr. Dayan Goodenowe will be leading the community “SaskTrial” for the prevention of neurodegenerative disease.

You can read Dr. Goodenowe’s findings in the Relation of Serum Plasmalogens and APOE Genotype to Cognition and Dementia in Older Persons in a Cross-Sectional Study. Dr. Klings findings will be released in the The Journal of the Alzheimer’s Association this summer.

You can also watch both scientists discuss the IKU collaboration in The NeuroDRO — End Alzheimer’s and The Plasmalogen Hypothesis video series that we recorded in Factory Berlin and Prodrome Health Centre.

Dr. Dayan Goodenowe discusses the IKU NeuroDRO

Dr. Mitch Kling and Dr. Dayan Goodenow discuss the plasmalogen hypothesis

The IKU NeuroDRO

In the spirit of shaking things up, both scientists have decided to lead a decentralized research organization and offer the IP/commercial royalty of the supplement, as well as the supplement itself, to first comers of the IKU platform. Not only are Goodenowe and Kling willing to put their names on the line and test human efficacy of synthesize plasmalogen in a clinical trial, they both are advocates of open science and want to make all associated research data available in the NeuroDRO. You will need a NEURON Token to access and/or license the data. Read more about the IKU model here.

And perhaps that is what is necessary to achieve more than what industry has done to date. The will to risk and pursue something different. To break down the traditional walled gardens and offer the data to society, to benefit the world. Something industry is terrified in doing and losing a buck.

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