$AVXL Parkinson, Alzheimer and Homeostasis Claim on ANAVEX 2-73

Parkinson’s and Alzheimer

I did some reading on Parkinson’s on Wikipedia and was looking for common thread here with Alzheimer.

Let’s start with Alzheimer (AD).  The cause is unknown.  Weak genetic connection. Those who carry genes connected with AD have 10% probability to have the familial form of the disease (vs. sporadic (no genetic connection)).  It seems that the occurrence is due to epigenetics or what is called molecular roulette.  Currently, the plaque (Aβ and Tau) are the biomarkers for AD, yet one-third deceased patient with AD symptoms are plaque free. It is possible that the current biomarker is just a link in chain of events and not the cause of the disease. Murine models (transgenic, carrying the Swedish Mutation) point to onset of mental decline before appearance of plaque.  Loss of neurons connected to presence of microglia in affected brain tissues and inflammation.  At the moment, the therapeutic targets are the plaque and neurotransmitters (Donezepil) to treat symptoms not the cause and temporary at that.

Then Parkinson’s disease. The cause is unknown. Weak genetic connection (cases of familial vs sporadic). Epigenetics and exposure to insecticides blamed.  Aggregation of alpha-synuclein, a protein involved in physiology of synapses, just like the plaque.  Loss of neurons involved in motor control and microglia presence in affected tissues (inflammation?).  Lewy Bodies as biomarker (histology).  Loss of neurons producing dopamine; compensation by attempting to bring the levels up only temporarily alleviating symptoms.

The buzzword used by Dr Missling was homeostasis, to anchor the therapeutic effect of ANAVEX 2-73 to reference of something well-known in medicine.  The only problems is that homeostasis does not exist as something “material”.  If we assume that there are 500 thousands of all kinds of protein, lips, sugars and whatever else in your body, in cells and around them, then the statistical probability of interactions which might be harmful to your health is staggering.  Human beings build mechanical, electrical and electronic devices and in everyday life we see their failures.  Have you ever had product which did not occasionally break down and had to be replaced?  When there was the moon landing the probability of failure was assessed to be 50%.  Amazingly, the health of machines run by organic chemistry is way more complex and also by extension exponentially more on statistical level exposed to danger of break down then these simple physical devices we build. The apparent paradox was removed by the concept of homeostasis i.e. self-regulation.

The extent to which one particular organic molecule can be involved in your health can be overwhelming to any simplistic approach. When you read about the current state of knowledge on some of them you see that they are implicated in number of cascades, tissues and organs.  Look, in how many places or tissues or cascades is implicated cholesterol.  If you are after something in physiology you try to limit the scope of the system in experiment so that secondary effect are not making the interpretation of results too difficult.  But then in real life, how many drugs turned harmful or riddled with severe side effects when introduced into living and breathing patients.  These cascades crisscross each other, regulating others or running feedback loops within themselves to create a complex system of interaction which calls into existence bioinformatics out of necessity to chart overwhelming to our minds amount of connections and interactions.  Evolution has built immensely complex systems of check and balances, to borrow term from the realm of politics, to guard against processes running amuck. Complexity theory would call the paradox of  health of living things despite their statistical probability of disturbance (sickness) an emerging quality i.e. homeostasis.

Calling on homeostasis in case of ANAVEX 2-73 is one bold claim.  If indeed there is meat on the bone here then ANAVEX 2-73 has illustrious career ahead of it.  Would PD be next falling domino?

The history of medicine is the history of emerging opportunities to address the causes of diseases with information every expanding.  In case of AD or PD the current knowledge moves from the biomarkers of Aβ, Tau and dopamine (PD) i.e. known ones to cellular homeostasis (mitochondria health, glucose metabolism, Ca+ channel, oxidative stress) to inflammation (system wide response to disturbance).  The first discoveries were on the level of histology (what can be seen changed in tissues and cells under microscope (XIX and XX century)) now they move toward the peripheries (from that location) to organic chemistry of CNS cells and immunology of CNS (system response).

In case of AD donezepil and in case of PD L-dopa, these are the attempts to replace what can at the moment be measured or detected, or lack of it, and these were the neurotransmitters respectively involved in memory and motion processing.  Both only address symptoms and temporarily for that.

Let me make a case for Unknow Scientist.  The amount of papers written is astounding, they move us inch by inch toward greater understanding so that One Fortunate Scientist can “put it together” and get lionized in main stream media as a genius, great discoverer. In hind sight everything was predictable to some extent as always somebody turned out to be prescient to bet on wild horse.  When your bet pans out it all falls into place and you are celebrated, may be even envied, before that you are a hopeful fool ignored and despised.

Brain Model

 

 

 

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