Anavex Life Sciences Corp (AVXL)

[XenaLives]

Compiled: MOA and MEDICAL SCIENCE DISCUSSION 07/12/19
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Some FYI from the 5/19 10-Q regarding the science.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148704240

What is autophagy (from Pennydouble):

Eventually, It Will Be Anavex Prophylaxis
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148461516
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148463672

A nice blog giving an overview of neurotransmitters:
https://poweronpoweroff.com/blogs/longform/a-guide-to-neurotransmitter-balance

Researching glutamate induced cytotoxicity, article:
https://www.frontiersin.org/articles/10.3389/fncel.2015.00091/full

From kevli33 - a blast from the past:
Jan 2018 Webcast of " Central Nervous System: Is there a cure for Alzheimer’s on the Horizon? "
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146009833

Fire station analogy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=144927755

Anavex MOA described -
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145657588

Hampel's August 2018 statement on the action of 2-73:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145787370

Sokol gives us scientific studies to support 2-73 restoration of cellular homeostasis:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145694010

The Unique Anavex Mechanism of Action and why it works differently than Donepezil
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145634041
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145648700
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146528112

Drug binding and efficacy are not the same :
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=138603679

Protein Misfolding and ER Stress in Huntington Disease (from georgejjl)
https://www.frontiersin.org/articles/10.3389/fmolb.2019.00020/full

BDNF, Sigma-1, and Huntington Disease
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149255300

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Sigma-1:

Dr. James E. Barrett Ph.d., from Drexel Univ. at the Univ. of New England -
UNECOM Biomedical Research Seminar
Sigma-1 Chaperones for the Treatment of Pain, Neurodegenerative Disorders and substance Abuse
Pre 084 is among those looked at.

From tradeherpete, comments on the above:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149667334

PubMed index of info on sigma-1 receptor from kevli33:
https://www.ncbi.nlm.nih.gov/pubmed/?term=sigma-1+receptor

Sig-1R and exosomes:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=14293179

Deep dive into history of Sigma-1 Receptor - the start of a good discussion by several posters, do read forward from here:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149338341
Comments on the above:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149339271
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=149339973

The Roles of Intracellular Chaperone Proteins, Sigma Receptors, in Parkinson's Disease (PD) and Major Depressive Disorder (MDD).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6537631/

Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor/sigma1 (s1) ligand ANAVEX2-73, a novel aminotetrahydrofuran derivative (from georgejjl)
https://www.researchgate.net/publication/46191396_Anti-amnesic_and_neuroprotective_potentials_of_the_mixed_muscarinic_receptorsigma1_s1_ligand_ANAVEX2-73_a_novel_aminotetrahydrofuran_derivative

What the Sigma-1 receptor does:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145690421

What the Sigma-1 receptor is:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145774636
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147249382

Sigma-1 Receptor as a Pluripotent Modulator in the Living System
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147249865

Broad application of the Sigma-1 (from georgejjl)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158303/

Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases.
(2017 article from mapman1010)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603014/pdf/12929_2017_Article_380.pdf

Article 4/23/19
Sigma-1 Agonists Offer Combination Approach to Dementia Symptoms
Research from the past decade suggests that sigma-1 receptors and their encoding gene, SIGMAR1, together act as a therapeutic target for patients with dementia.
Published: April 23, 2019 Contributed by Mikesc
https://www.neurologylive.com/journals/neurologylive/2019/april-2019/sigma1-agonists-offer-combination-approach-to-dementia-symptoms

Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo
Published: 2 March 2019 - free full text access now available (from nidan7500 )
https://www.mdpi.com/2073-4409/8/3/211/htm

What may set AVXL 2-73 apart from other S1 receptor agonists.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145782971

November 2018 publication on Sigma-1 - note the dates of publication history starting in 2016:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771390/pdf/CN-16-97.pdf

Dr. Tangui Maurice on the Sigma-1 - 2015 video:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143980208

History of the Sigma-1 Receptor:
molpharm.aspetjournals.org/content/89/1/142

Sigma-1 in Cancer
https://www.ncbi.nlm.nih.gov/pubmed/23988449
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274865/

Myristic acid hitchhiking on sigma-1 receptor to fend off neurodegeneration (fom georgejjl)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827442/

SIGMA-1 RECEPTOR AGONISM: THE NOVEL TREATMENT OPTION IN RENAL DISEASE. Ádám Hosszú
https://docplayer.net/96707227-Sigma-1-receptor-agonism-the-novel-treatment-option-in-renal-disease-adam-hosszu.html

How the Sigma-1 affects every cell in the body:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146258203
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MUSCARINIC RECEPTORS:


M1 Muscarinic Receptor Activation Rescues ß-Amyloid-Induced Cognitive Impairment through AMPA Receptor GluA1 Subunit. (from georgejjl)
https://www.ncbi.nlm.nih.gov/pubmed/30981860

M1 Muscarinic Receptors Modulate Fear-Related Inputs to the Prefrontal Cortex:(from georgejjl)
https://www.ncbi.nlm.nih.govThi/pubmed/31003787

The M1 muscarinic acetylcholine receptor subtype is important for retinal neuron survival
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148297709

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AUTOPHAGY:

NEWS!!! March 4, 2019 Third party paper on cellular recycling.
https://www.anavex.com/anavex-life-sciences-reports-publication-of-new-data-that-show-anavex2-73-induces-cellular-recycling-process-linked-to-the-prevention-and-treatment-of-age-associated-diseases/

Access to above paper
https://www.mdpi.com/2073-4409/8/3/211/htm

What is proteostasis?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147258047

Summaries of the autophagy paper:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147424647
https://parkinsonsnewstoday.com/2019/03/07/study-reveals-neuroprotective-mechanisms-anavex-2-73/

What is autophagy? (from nidan7500) video from Investor 2014.
https://www.news-medical.net/health/What-is-Autophagy.aspx

This MOA applies to the aging process in general:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147257995
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147361303

Modulation of autophagy by BDNF underlies Synaptic Plasticity
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147538457

Now we have the Firetruck and Garbagetruck (from Investor2014):
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147358699

Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders.
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147423046

A series of posts on autophgy from georgejjl
#184496 Autophagy and mitophagy in ALS.
#184495 New preclinical data establishes ANAVEX®2-73 as a modulator
#184494 Role of autophagy in the pathogenesis of multiple sclerosis
#184493 Dysregulation of autophagy and mitochondrial function in Parkinson’s disease
#184492 Impairment of the macroautophagy: a possible hallmark of
#184491 Elimination of ß-amyloid plaques via macroautophagy
#184490 Protein Misfolding and Accumulation as Root Cause in Neurodegeneration
First post in series: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147417660

There are no posts mentioning autophagy on this board prior to 2015.

2015 posts mentioning autophagy - one each from georgejjl and TrueTrades:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=118317394&txt2find=autophagy
Link to the entire paper referenced by TrueTrades:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807076/pdf/mol.113.087809.pdf

2016 posts mentioning autophagy - three from georgejjl:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=121979414&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=122985309&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=126356651&txt2find=autophagy

Potential Roles of Mitochondria-Associated ER Membranes (MAMs) in Traumatic Brain Injury (from george jjl in 2017)
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=129858549

Autophagy not mentioned again until two posts on 3/9/18 by mapman1010.
It's interesting that it was almost precisely one year before the current paper:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=139184780&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=139185523&txt2find=autophagy

Discussion of the above:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=140322574&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=140431749&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=140576574&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=140709556&txt2find=autophagy

Autophagy other 2018 mentions:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141039429&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141231591&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141689338&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141909594&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141925525&txt2find=autophagy

ER–mitochondria signaling in Parkinson’s disease (from mapman's link to article post below)
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142355746&txt2find=autophagy
PDF of the article cited:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832754/pdf/41419_2017_Article_79.pdf

Autophagy and late Alzheimer's:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143131392&txt2find=autophagy

Amateur17 linked to this article on research done in Australia in 2018:
Alzheimer's tied to brain's 'waste removal system'
https://www.medicalnewstoday.com/articles/322857.php

Sokol post touches on the subject and gives a comprehensive overview of research:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143320176&txt2find=autophagy
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143320176&txt2find=autophagy

Autophagy was discussed in September 2018 at the New York Academy of Sciences one-day symposium
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=143337580&txt2find=autophagy

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=145735099&txt2find=autophagy
The above links to non public research by Ashutosh Kumar, I found these links:
https://www.eurekalert.org/pub_releases/2018-12/bsp-aam122618.php

More on Dr. Kumar and his line of research:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147423162

Posts on autophagy and mitochondrial dysfunction studies being done by Dr. Ashutosh Kumar
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147422690
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147423162
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BDNF:

"AdministraCon of ANAVEX 2-73 in the Fragile X Fmr1 KO mouse significantly restores hippocampal BDNF expression to the same levels observed in vehicle-treated wildtype mice (p<0.05, KO vehicle vs. KO ANAVEX 2-73)" slide of the presentation below:
http://www.anavex.com/wp-content/uploads/2017/05/Anavex-Angelman-FX-Rett-conference-update-2017-May-2017-final.pdf

What is BDNF?
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148132680

ANAVEX 2-73 Normalizes Hippocampal BDNF Expression
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148132992
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ENDOCANNABINOID SYSTEM:

National Institute on Drug Abuse (NIDA/NIH) 2016 pesentation on the endocannabinoid system (>1 hr)

From dadofmarcmax 10/24/18
HOMEOSTATIC NETWORKING: THE ROLE OF PHYTOCHEMISTRY, THE ENDOCANNABINOID SYSTEM AND POTENTIAL FUTURE THERAPEUTICS
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=144438361

Comments on Cbd and Anavex from Cbdpotential:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146337883

Cannabanoid receptors
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146262610

dadofmarcmax on endocannabanoid system:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=144438361
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MITOCHONDRIAL DYSFUNCTION:

see also genetics section

Commonly prescribed drugs are tied to nearly 50% higher dementia risk in older adults, study says (from kevli33).
https://www.cnn.com/2019/06/24/health/dementia-risk-drug-study/index.html

Mitochondrial dysfunction as a result of drugs and man made environmental toxins:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142383333

ROS, mitochodira, and 2-73
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142698154

Protein Misfolding and Accumulation as Root Cause in Neurodegeneration:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=1474176602-73

Misfolded proteins in cardomyopathy:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=148733003

Dangerous medicines and mitochondrial dysfunction:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=142393634

Fluoroquinolones, benzodiazapenes, GABA, motochondiral damage:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146867284
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146867900

Mitochondrial dysfunction, calorie restriction, aging, evolution and genetics:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821041/

Could Disposing of Damaged Mitochondria Treat Alzheimer’s Disease? (from Investor2014)
https://www.alzforum.org/news/research-news/could-disposing-damaged-mitochondria-treat-alzheimers-disease

Autism and Mitochondrial dysfuncution
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147104490

CVD and mitochondrial dysfunction:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=146829394&txt2find=neurotransmitters

Envoiromental and pharmaceutical causes of mitochondrial dysfunction COMT gene:
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147602552
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147602754
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=147603103