Homeostasis and Why This May be A Reasonable Focus
The human body is the most complicated structure that I know of and composed of a myriad of interconnected, yet different processes – many of which are controlled by feedback loops – just as the heating/air conditioning system in your home is controlled with a feedback loop regulated by the thermostat.
Briefly – the state of a neuron (or cell in general) is not an “all or nothing” endeavor – i.e. a neuron is not either dead or alive. A neuron, can be still partially functional (dysfunctional is a rather more appropriate term) when injured and dying – i.e. a “sick” neuron so to speak.
In the setting of neuronal insulations – a cascade of events take place often involving neuroinflammation (I have covered this, at length on YMB and Ihub to a lesser degree in the past) that often times end in neuronal death. Falconer66, whose posts have been most informative recently, has correctly described the process of mitochondrial-endoplasmic reticulum (ER) dissociation whereby the ER no longer can effenciently use the power supplied by the mitochondria to regulate internal neuronal/cellular processes often involving protein misfolding, etc.
When a large aggregate of neurons are chronically exposed to the neuroinflammatory cascade of events – there begins a futile cycle of neuronal death, inducing more neuroinflammation that in turn leads to further neuronal death – chronic neurodegeneration and depending on the regions of damage – may lead to Alzheimers dementia, other types of dementia, Parkinsons Disease (PD -if the basal ganglia/midbrain dopaminergic structures are involved), etc. The theory being that there is one complicated neuroinflammatory process that results in a multitude of different neurological pathologies.
What if there is an agent that can perhaps stop the herald steps of this complicated neuroiflammatory cascade that can lead to the different pathologies (that seem to result from a similar pathophysiological process)? What if this agent can allow a dysfunctional neuron, with disordered and dysfunctional mitochondria/ER regulation – to allow for the neuron to function more normally – restoring homeostasis? The theory, further advanced, suggests that if the chronic insulting process – chronic neuroinflammation – is halted, the body’s natural – “self healing” processes can supercede the degenerating processes caused by the futile cycle of chronic neurodegeneration.
In my opinion, this is why AVXL is so different from the other companies working in the Alzheimer’s space with the hackneyed “clearing of beta amyloid plaques” approach. It is more worthwhile, in my opinion, to target the processes that cause the plaques to develop in the first place. The plaques, being end products of misfolded proteins causing them to be insoluble, are not the cause of cognitive decline and why, I believe, this conventional approach taking by Lilly and Biogen is bound to fail.
Restoring natural cellular homeostasis is why I believe Anavex is at the forefront to the paradigm shift in treating neurodegenerative disorders. The company is small, it is promoting a theory that has never been promoted before by the top researchers in Alzheimers and in big pharma. The Semmelweis reflex is truly in effect with Anavex.
Semmelweis reflex: the tendency to reject new evidence or new knowledge because it contradicts established norms, beliefs or paradigms. The bias takes its name from the reaction of the medical community against the findings of Semmelweiss, the Hungarian physician who showed that hand-washing by physicians in an antiseptic solution before delivery reduced puerperal sepsis in the mother by 90%.
Good luck to all the long investors!
AI
