Replies to post #252341 on Anavex Life Sciences Corp (AVXL)

[nidan7500]

https://sciencing.com/aging-affect-ability-restore-homeostasis-22809.html

sokol

Yes, Missling describes it as: “ANAVEX®2-73 (blarcamesine) is an orally available, small-molecule activator of the sigma-1 receptor which, data suggest, is pivotal to restoring neural cell homeostasis and promoting neuroplasticity.”

https://www.anavex.com/anavex-life-sciences-issued-new-u-s-patent-for-composition-of-matter-covering-anavex2-73-for-the-treatment-of-alzheimers-disease/

“Living organisms need to maintain homeostasis constantly in order to properly grow, work, and survive. In general, homeostasis is essential for normal cell function, and overall balance.”
https://www.bioexplorer.net/importance-of-homeostatis-examples.html/#Importance_of_Homeostasis

Exceptional post Sokol. Thank you.

[Jonjones325]

Excellent post. Like you said our drug and the way it interacts with the sigma 1 receptor may show improvements in people in varied ways.

So we are using the CDR as our primary endpoint and the actigraph along with other tools to measure 2-73s effectiveness.

It’s hard to believe but I guess theoretically a person can fail at these endpoints but feel improvements in a whole host of other areas since the receptor is prevalent throughout our bodies. So, I don’t sleep any better and my cognitive deficiencies are still there and possibly decking but my blood pressure is better, my eyesight has improved, etc.

Like others have stated before, it’s hard to see these improvements without the improvement of sleep in conjunction.

[jmvho]

Great post sokol !!

jmvho

[sokol]

Why the 2-73 PDD results may be positive.


Autophagy is involved in maintaining cellular homeostasis and that may be key to treating PDD.


"As brain changes caused by Parkinson’s gradually spread, they often begin to affect mental functions, including memory and the ability to pay attention, make sound judgments and plan the steps needed to complete a task....


The key brain changes linked to Parkinson’s disease and Parkinson’s disease dementia are abnormal microscopic deposits composed chiefly of alpha-synuclein, a protein found widely in the brain with a normal function not yet known. The deposits are called “Lewy bodies” after Frederick H. Lewy, M.D., the neurologist who discovered them while working in Dr. Alois Alzheimer’s laboratory during the early 1900s...."


https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia/parkinson-s-disease-dementia#about


"Alpha-synuclein is normally a wavy-like structure and in Parkinson's, the alpha-synuclein protein misfolds forming a toxic clump or aggregate.....They also go on to accumulate in large masses termed 'Lewy bodies' and these clumps are now associated with brain cell death; the process involved in the aggregation of these misfolded proteins may be a trigger for PD...Alpha-synuclein, like all other proteins produced in the cells of the body is subject to regulation and recycling and sometimes it is the failure of this process that may lead to aggregation....


Although scientists do not know exactly what causes the protein to misfold and clump together, many believe that if we find a way to prevent its accumulation or reduce alpha-synuclein gene expression or promote its removal and or recycling , we may be able to stop and potentially reverse the damage these deposits may cause to the brain. It is not surprising then that alpha-synuclein has now become a major target for potential PD therapies."

https://www.cureparkinsons.org.uk/why-alpha-synuclein


"....Autophagy is involved in maintaining cellular homeostasis......". See Regulation and Function of Autophagy during Cell Survival and Cell Death
https://cshperspectives.cshlp.org/content/4/6/a008813.full


"...ANAVEX®2-73 can selectively induce the autophagy process and increase protein homeostasis in both in vitro and in vivo models...


Autophagy is a cellular process that cleans cells of defective proteins and is part of a set of mechanisms that participate in proteostasis, or the balance of the protein network. Loss of proteostasis and dysfunction of the autophagy process, has been closely linked to the pathogenesis of human neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and ALS1.


“There is a great amount of data linking dysfunction and malfunction of autophagy to neurodegenerative disease and, consistent with its role in proteostasis, to the accumulation of protein aggregates. Thus, the modulation of autophagy has become one key pharmacological target in neurodegeneration,” the researchers reported. “In fact, there are multiple overlaps of autophagy and pathogenesis pathways in Alzheimer’s disease, Parkinson’s disease, and ALS. Recently different alternative views and new pharmacological targets towards Alzheimer’s prevention and treatment are evolving and include a strong focus on the autophagy process.


The Cells paper also noted that this is the ?rst report to show that Sig-1R activation enhances the autophagic ?ux in human cells and in C. elegans with positive effects on proteostasis in vitro and in vivo, an important concept towards the stabilization of neuronal survival and function that may help to prevent age-associated neurodegeneration."


https://www.globenewswire.com/news-release/2019/03/04/1745838/0/en/Anavex-Life-Sciences-Reports-Publication-of-New-Data-that-Show-ANAVEX-2-73-Induces-Cellular-Recycling-Process-Linked-to-the-Prevention-and-Treatment-of-Age-Associated-Diseases.html


See also my post: How may AVXL 2-73 benefit patients with Parkinson's dementia? https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149155921

Lastly, AVXL 2-73 as a Muscarinic agonist affects short term memory (paying attention, etc.) and long term memory whereas Sigma 1 may only be involved in long term memory.