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ANAVEX 3-71

alzheimer’s disease amyloid and tau pathologies

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#1 alc

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Posted 07 December 2015 - 11:20 PM


From their web site:

 

"The ANAVEX 3-71 data provides evidence for a positive, more upstream effect on reducing synaptic loss, amyloid and tau pathologies, and neuroinflammation, which is potentially beneficial for the treatment of Alzheimer’s and other neurological diseases. ANAVEX 3-71 is part of the Company’s pipeline including ANAVEX 2-73 targeting sigma-1 and muscarinic receptors.

“Our preclinical findings for ANAVEX 3-71 demonstrate its significant potential to enhance neuroprotection and cognition via concomitant activation of sigma-1 receptor and M1 muscarinic acetylcholine receptor (M1R), which could be a therapeutic advantage in treating Alzheimer’s and other related protein-aggregation diseases,” said study author Abraham Fisher, PhD. “Specifically, the study results reveal that ANAVEX 3-71 effects a strong reversal of synaptic loss in hippocampal neurons. At very low doses, it mitigates cognitive deficits and normalizes major pathological hallmarks in Alzheimer’s disease models indicating that ANAVEX 3-71 exerts a comprehensive disease-modifying effect. This data adds to the strong foundation of preclinical evidence to support the potential use of ANAVEX 3-71 in Alzheimer’s disease and a wide array of other central nervous system diseases.”

 

http://www.anavex.co...-disease-models

 

 

also from their web site

 

"Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s disease. It has also exhibited anticonvulsant, anti-amnesic, neuroprotective and anti-depressant properties in convulsive epileptic animal models, indicating its potential to treat additional CNS disorders, including epilepsy and others. Michael J. Fox Foundation (MJFF) for Parkinson’s Research has awarded Anavex a research grant to develop ANAVEX 2-73 for the treatment of Parkinson’s disease to fully fund a preclinical study, which could justify moving ANAVEX 2-73 into a Parkinson’s disease clinical trial. ANAVEX 3-71, also targeting sigma-1 and M1 muscarinic receptors, is a promising preclinical drug candidate demonstrating disease modifications against the major Alzheimer’s hallmarks in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid and tau pathologies, and also with beneficial effects on neuroinflammation and mitochondrial dysfunctions."

 

 

 


Edited by alc, 07 December 2015 - 11:23 PM.


#2 HighDesertWizard

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Posted 08 December 2015 - 02:40 PM

alc... The link you provide is a great find about Alzheimer's.

 

Our preclinical findings for ANAVEX 3-71 demonstrate its significant potential to enhance neuroprotection and cognition via concomitant activation of sigma-1 receptor and M1 muscarinic acetylcholine receptor (M1R), which could be a therapeutic advantage in treating Alzheimer’s and other related protein-aggregation diseases,” said study author Abraham Fisher, PhD. “Specifically, the study results reveal that ANAVEX 3-71 effects a strong reversal of synaptic loss in hippocampal neurons. At very low doses, it mitigates cognitive deficits and normalizes major pathological hallmarks in Alzheimer’s disease models indicating that ANAVEX 3-71 exerts a comprehensive disease-modifying effect. This data adds to the strong foundation of preclinical evidence to support the potential use of ANAVEX 3-71 in Alzheimer’s disease and a wide array of other central nervous system diseases.

 

Is there a larger physiological/biological significance to the findings supporting the use of ANAVEX 3-71?

 

I've said it before and I'm happy to say it again. To this date, Longevity Science Movement Thought Leaders are generally uninformed about the importance of the Vagus Nerve, Heart Rate Variability (HRV), and the Cholinergic Anti-Inflammatory Pathway (CAIP). CAIP activation has a profound impact on NF-kB Nucleus Translocation and Transcription of Inflammatory Cytokines. This pathway has implications for Survival in Humans as shown in the graphic figure pasted in below.

 

We understand a lot about the Mechanism of Action. Specifically, we know that...

  • Activation of the M1 Muscarinic Acetylcholine Receptor by Vagus Nerve Stimulation and/or pharmachological means triggers the CAIP. Last week, I posted about another M1 Muscarinic Acetylcholine Receptor agonist, a drug, Xanomeline, that also has positive benefit for Allzheimer's Disease and for Schizophrenia. It also has implications for Survival--see the Survival Curves at the link--and we understand something about dosing schedule (see link in this bullet paragraph).
  • Heterochronic Parabiosis scholars Villeda and Wyss-Corey have found that pCREB and c-fos activation are the immediate mechanism for rejuvenating cognition in mice. This confirms the importance of the M1 Muscarinic CAIP mechanism that Kevin Tracey has been writing about for 15 years. Details and graphic figure summaries can be found here.
  • The Physiological Science of the CAIP provides an explanation about why even a very small dose of ANAVEX 3-71 could "mitigate cognitive deficits and normalize major pathological hallmarks in Alzheimer's disease models..." Per the work of Tracey and others, M1 Muscarinic Acetylcholine Receptor agonists trigger a CAIP Mechanism that Requires Intact Vagus Nerve and Splenic nerve processing. My hunch is that NF-kB Inhibition within the Spleen by this Vagus-Acetylcholine mechanism is The Primary Physiological Means by which Rejuvenation of Blood Factors within the Circulation takes place. Here are two simple graphic figure from Tracey's great 2007 state of the knowledge summary. Tracey had nailed the importance of the M1 Muscarinic Nicotinic Acetylcholine Receptor by 2007...

JCI0730555.f2.jpg

Here's the Human Survival Curve I promised above. It appears in the opening post of this thread.

 

Here’s the study context... Take a known Surrogate Marker for Health, it’s a Computed Statistic... Measure this marker for 24 hours in old, wild-type Humans, 65 years old and up with a mean of 73 years… Wait 10 years… 53% of the 347 study animals are now dead... Do some statistical analysis of that surrogate marker data and plot the two survival curves below… That marker, Heart Rate Variability (HRV), has profound implications for human health and longevity... Here’s a link to this study from 1998...

 

d8RicwD.png


Edited by HighDesertWizard, 08 December 2015 - 02:59 PM.

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Also tagged with one or more of these keywords: alzheimer’s disease, amyloid and tau pathologies

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