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Back Then, I Didn’t Believe (Or Understand), Either
In the late 1980s I was teaching Advanced Placement (college credit) biology in an Ohio high school. One of my students told me that I ought to buy some shares of “MicroSoft.”
I was actually using Microsoft hardware (an early Windows version of the time), on a computer with Microsoft software. My student (who went on to gain a doctorate in electrical engineering) said that in a few years the share price of the Microsoft stock would scale by orders of magnitude. A thousand dollars would appreciate to many hundreds of thousands, he was certain. (He was right, of course.)
What did I do with this smart kid’s Microsoft admonitions? “Well, Eric, that’s really interesting. Thanks. I’ll watch the matter closely.”
And that’s all I did.
I knew no more about coding, computer software, and the software and hardware market captures Gates and Company were accomplishing than people, today, know about Anavex or it’s otherwise arcane science.
If only...
Anavex Still An Unknown Entity
Altogether, Anavex is unknown, misunderstood, or simply neglected. Only the tiniest fraction of either the retail or institutional investor communities has even heard of some tiny company known as Anavex Life Sciences Corp.
For the few that have, comprehending the unique neurological science of the company is not worth the time to learn (if even possible). Without at least an undergraduate’s training in human biochemistry and cytology, the charts, diagrams, and descriptions of the Anavex sigma-1 receptor agonists and their molecular functions in neurons are simply confusing; if understood to even a slight degree.
Those of us who comprehend the Anavex science and have scrutinized its evidence are prone to wonder why ever more investors aren’t taking AVXL positions.
Simple. Not many, so far, comprehend the science; or don’t see that it will lead eventually to corporate revenues. Anavex is something most equity investors would have no personal reason to accumulate right now.
Wish it weren’t so. But until people start reading “real news, fit to print” about Anavex treatment successes in the New York Times (positive clinical results), nothing significant will change regarding public (investor) perceptions.
Just love the postings here, to the effect, “Well, if Anavex were so great and its science were so good, investors would be grabbing every share. They aren’t. So Anavex is a nothing.”
Common equity investors need to have their due diligence confirmed and authenticated by really smart people, such as the NYT writers. Watch what happens to the share price of AVXL after the first New York Times article on any sort of Anavex clinical trial result. Different world, then. But until then? More of the same, no matter what.
The Rats Have It. Anavex 3-71 Will Be Big
From this recent paper (4 Mar 2019):
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409318/
Yes, But MDs Won’t Control AVXL Share Price
Yes! Anavex, Lay Out The Long-term Findings.
The Political Factors of an Early Australian Approval
What, perchance, will be the politics of the Australians quickly approving the therapeutic use of Anavex 2-73 to treat or prevent Alzheimer’s? How might that get reported here in the US? That approval, alone will become an issue.
But the real issue will be when hundreds of Australian Alzheimer’s patients start taking the drug, with numerous reports of enhanced sleep, less irritability, and other favorable real world experiences.
How will FDA poobahs explain to news reporters that, “Well, we can’t have that drug here in the US. We don’t know if it’s really safe or effective. We want Anavex to first do a three-year study with 1000 Alzheimer’s patients.”
How might certain political personalities react? Especially should an election be near?
Alzheimer’s Inflammation Is Downstream; Anavex Is Upstream
But, Should Your “Saying” Guide All Investors?
Yes, in the third inning, in a pre-season game.
Confirms My Perception
The Science Itself, Not Its Explanation
That Seals It, Then. No Hope.
We Know What Will Happen
“Brain Swelling?” Get Real.
Volume Double
At around 10:32am volume eclipsed a doubling of the recent average daily volume.
Interesting (and, rewarding — I’m now in the green with my moderate AVXL holding).
Missling, Like Others, Knows It Won’t Fail
Why So Many Dollars Failed Against Alzheimer’s
It’s taken most of this century for firms with lots of dollars to come to the harsh realization that trying to treat Alzheimer’s with the moderately variable waste-clearing approaches (chemicals that induce immunological or direct chemical clearing of neurologically-toxic beta-amyloids or tau tangles) simply fail. How (or why) would otherwise intelligent, experienced scientists and their funders (big pharmaceutical firms, etc.) keep throwing so many millions (well, billions) of dollars at the same, failed-so-often process? Two or three times might be understandable. But 146 failures? What did these people learn in med school or schools of business administration that allowed so many, so expensive drug development mistakes?
As I see it (from a science standpoint; with no particular investment expertise), it appears that the prospects of giant payoffs masked reality. An eighth-grade science student could, in an hour’s clicking around the Internet, determine the fantastic corporate incomes that would be generated by any useful treatment of Alzheimer’s. Go for it! Pay so big, let nothing interfere.
People with the dollars (pharmaceutical executives) were certain that if they just hired the best-educated researchers, those deep-science types would find and develop real Alzheimer’s treatments. Like all other financial problems, they only needed money.
Only two Alzheimer’s treatment approaches were offered by the neurology science people.
One, inhibit acetylcholinesterase. With that, ample, useful concentrations of acetylcholine will be maintained in nerves, allowing their normalized, healthful function. That worked, actually, but only for short periods of time; whereupon the lethal progression Alzheimer’s progressed.
Or, much bigger and much better, somehow induce the immune system of the body to react with and dispose of waste beta-amyloids and/or tau tangles. They inhibit nerve function; cause Alzheimer’s symptoms.
But that never worked, in any of the concept’s iterations. Too many debilitating adverse events (side effects), or simply poor clearance of the toxic waste proteins.
The drug companies, for several decades, have followed the Thomas Edison method of new-concept product development. Keep throwing things at Alzheimer’s neurons and eventually, something will stick and work. For light bulb filaments, that worked. Edison tested hundreds of materials before finding a form of bamboo from Japan that worked.
Neurons with Alzheimer’s (well, and those without) are extremely complicated, with a multitude of chemical reaction pathways. The pharmaceuticals and their scientists tried to fix Alzheimer’s as though they merely needed to fix a burned out light bulb. Burned out neurons were the target.
But the approach was to restore neuron function by working at downstream disease stages. The toxins, mechanistically, were “downstream,” at the end of the pathogenic process. Like trying to re-attach already-broken light bulb filaments.
Anavex, instead, restores normalized neuron chemistries (proper protein folding, etc.) “upstream,” so that toxic waste proteins never accumulate. Instead of fixing burned-out neurons, Anavex molecules maintain neuron functions. With that (as the many preclinical and murine studies show), success.
I will be watching closely, to see how the media explain the positive clinical results later this year. How will they explain to the public how the Anavex sigma-1 receptor agonists actually work. Their biochemical functions are very complex; difficult to understand (or convey) without a rather deep understanding of neuron physiology and morphology. A wonderful problem to be presented with.
“Dr. Missling, our viewers here at CBS want to know the magic of your new drug. The new clinical results are astounding. Tell us how it works. Until now, nothing else has. What’s your secret?”
Anavex Science Now Being Seen --- Great Future
I'm delighted to finally see the increase in volume and share price. I'm no equity trader type; just a science guy.
In any number of posts I've been explaining the profound Anavex science; how it really fixes (or prevents) any number of central nervous system diseases and conditions (along with a yet undiscovered number of other sorts of diseases). Until the last few weeks, smart money people (self-defined) made it clear here on IHub and elsewhere that the Anavex story was bogus. "No evidence." "No known mechanism of action." "Insufficient clinical data." Etcetera.
Those laying out reasons to stay away from buying any AVXL shares have been strangely quiet. Now, there is evidence; and it matches almost exactly what I claimed for the Anavex molecules in previous years.
I'm smiling, with a degree of satisfaction. The Anavex science I tried to detail is no longer in question.
Next, will my conjectures of expansive Anavex Life Sciences Corp revenues appear in the same manner, matching my projections from some time ago?
(Wish I had some more funds. But I'm fully accumulated in AVXL. Moderate position, that will in a decade be very, very rewarding.)
Best wishes to all who have hung on to their shares. The Anavex ship has left the dock and set sail. No other CNS disease "ship" like it.
Indication of Future Value
The strong admonitions of Anavex management to vote to affirm the preferred shares, to obviate or discourage a hostile takeover by another pharmaceutical (however that will work) confirms to me that management knows of, is assured of the company’s gigantic financial future. In a decade, they want full value for the shares they own. They don’t want a cheap, quick low-value buyout, either for themselves or us shareholders.
Good for them. Good for us.
Science Essentially Irrelevant to Share Price
I did a first-look read through of today’s new Anavex PDF. The science is all there, in rather complete and detailed form (for those who can understand it). We haven’t been seeing many of the formerly-frequent postings telling how the (then) purported “science” was both impossible and unsupported.
It’s clear. The validity of the unique (and proprietary) science of the Anavex molecules will in no way elevate or drive the AVXL share price. Now, only one thing counts: Will Anavex Life Sciences Corp eventually be able to sell drugs and make a profit?
That, of course, will be known only when positive results are revealed in any one of the three clinical trials now under way.
Later this year.
No, Anavex Molecules Won't Fix Everything
I don't see how Anavex molecules could prevent bacterial or viral infections. Can't fix systemic poisonings. Can't fix diseases caused by nutritional deficiencies.
Won't be a cure-all. But might be a prevents-much, and fixes some big aging problems.
The Anavex “Iceberg” An Entire Floating Glacier?
Yes, the ability of both of the lead Anavex sigma-1 receptor agonists, Anavex 2-73 (presently) and Anavex 3-71 (in later trials) to yield positive therapeutic outcomes for a wide diversity of diseases is high. Presently, the focus is only on the three central nervous system diseases being targeted in the human clinical trials being arranged and initiated: Rett syndrome, Parkinson’s disease, and Alzheimer’s. Any sort of therapeutic success with any one of that trio will make Anavex Life Sciences Corp a profit-making concern. But a very high probability that all three will yield favorable treatment results.
It is important to understand that so many other diseases and conditions share the root pathogenic dysfunctions addressed in the new paper; poorly-functioning autophagy, allowing toxic wastes to accumulate. The Anavex molecules restore functional sigma-1 receptor activities.
As I’ve conjectured before, I’m rather certain that Missling and the other Anavex principals know full well the potentials of their molecules. It was inadvertently from that understanding that Missling made the “tip of an iceberg” comment.
I’m eager to learn what a generalized dosing regimen of either of the molecules might do to prevent or suppress many (or most?) of the debilities that accompany otherwise normal aging. In that case, Anavex would be prescribed as a prophylactic, a generalized preventative; before any actual symptoms are presented. I’m hypothesizing that the Anavex molecules will have their best effects when administered before any symptoms appear; before cellular physiologies have been grossly disrupted (the full-symptom disease state).
Anavex therapies before symptoms present. With that, how many geriatric disease states could be stopped or delayed?
Part of that might well be by the very positive outcomes of enhanced sleep patterns and durations that the Anavex molecules appear to so safely induce.
Let’s watch all of this. A big but melting iceberg (good enough)? Or, a pair of molecules of glacial size aspects?
Here's the story.
Don't Know
"Like the difference between say Reuters vs. Fox News?"
Nah. More like the New York Times and the Boston Globe.
Beyond Me.
Yes, The Anavex Story Is Way Bigger
Ok, the Buy-out Factor
Mechanism of Action Notwithstanding...
Now that the mechanism(s) of action of Anavex 2-73 have been independently elucidated and confirmed in a paper in a major peer-reviewed journal, the formerly so-frequent cautions that it’s not really known either if or how the drug works, will be (thankfully) infrequent. Those who throw that argument against Anavex Life Sciences Corp wall will find it no longer sticks. Instead, the mud of that now-negated argument will soil the accusers’ shirts. No longer a factor.
Nonetheless, the paper’s findings, per se, are not likely to promote any significant AVXl share price elevation. They may help create a higher low-end price resistance floor, as those who have accumulated AVXLs now have firm assurance that the drug works and will, eventually, gain and have applications that will make Anavex Life Sciences Corp a revenue-generating entity.
But, frankly, the vast majority of equity investors, whether mom-and-pop retail types, or even big institutions, simply can’t (or won’t) read and understand the arcane biochemistry and cytology of the paper. The only thing taken away from it by most is that, yes, Anavex 2-73 really does work, and by otherwise inscrutable methods those white lab coat guys understand.
All of that merely creates, perhaps, a new, slightly higher share price floor. Many might be hoping that the paper will propel AVXL much higher. I doubt it. Equity buyers, whether individuals or institutions, buy shares only in anticipation of their growth in value. The new paper, by itself, won’t bring any new revenues to Anavex Life Sciences Corp. That will happen only when the company gets the approval to sell Anavex 2-73 somewhere, for something (perhaps Australia first).
And that won’t happen until drug regulation agencies see positive clinical results from any one of the tree trials getting under way. As exciting as the information in the paper is, it won’t, by itself, significantly propel the AVXL share price. Simply, the market has to see people getting better after taking our drug. Then...? Watch out.
It Worked.
Anavex 2-73 Fills a Molecular Deficit, Fully Activates
I liked this statement from the paper:
Yup. Exactly!
Anavex 2-73 Works
Did a slow read of the abstract. Those who claim Anavex 2-73 lacks a known or operating mechanism of action against any central nervous system disease speak, now, in utter ignorance.
Can't Help
No, I have no useful knowledge of any of the cannabinoid molecules, neither of their constitution nor their modes of action.
I've encountered wild, remnant strains of Cannabis sativa in botanical field work back in the 1970s, in a Midwestern state. Those were remnants of hemp plantings, which in WWII were used to make rope (before modern synthetic fibers).
Yep, those plants looked exactly like marijuana. Some of my compatriot students surreptitiously "harvested" some of the leaves; to find that they had no psychotropic effects.
Autism and Mitochondrial Dysfunction — Potential Anavex Solution?
There is accumulating evidence that mitochondrial dysfunction is involved in many or most cases of autism.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467355/
In time, perhaps Anavex sigma-1 receptor agonists will be used to treat autistic infants, and perhaps suppress the progressive developments of the condition.
It’s The Anavex Molecules! The Stock Is Boring.
No, this stock is not exciting, in any way, or for any large group of investors. Boring, even dead (for the nonce).
But, yes, Anavex science is extremely exiting — utterly unlike anything in anyone else’s test tubes or lab rats. Totally new, unique, innovative, proprietary, efficacious disease treatment process. Will change 21st-century medicine more than antibiotics changed things in the last century.
Excitement with the stock will happen only when positive human clinical trial results appear later this year, either by anecdotal patient outcome leaks, or by a formal results release (most likely with the Rett girls first).
Epigenetics Too Complicated
I have a cursory understanding of the very hazy and yet poorly-understood (by everyone) subject of epigenetics. The concept a) is too detailed to usefully describe here, and b) I haven't enough understanding of its deep applications regarding disease therapy to make any description beyond the following.
I will make this conjecture. The Anavex sigma-1 receptor agonists appear to be able to cause normalized gene expression epigenetically; suppressing untoward genetic expression and promoting favorable gene expression (without affecting nucleotide sequences in situ, in vivo).
Anavex 2-73 Won’t Be “Gene Therapy;” Better
“Gene therapy” is generally regarded as the manipulation of nucleotide sequences, the deliberate changing of a gene’s genetic code. The code’s letters are Adenine = A, Thymine = T, Cystine = C, and Guanine = G.
A’s always (except in a mutation) connect to a T. C’s to G’s.
In gene therapy, now using CRISPR technology, new, improved, or fixed genes are inserted into the DNA of chromosomes, where the new nucleotide sequences, the chemical genes, code for proper peptides. Peptides are short, unfolded amino acid sequences. In the endoplasmic reticulum, properly-sequenced peptides are connected, making real proteins.
But in most cases, those proteins then have to be exquisitely folded into precise, complicated shapes to be functional. In most cases, the result is a functioning protein enzyme, which goes on to mediate and control virtually all of the cell’s chemistry.
First, sequence the amino acids properly, the function of the DNA code. Then, connect those amino acids in sequence. This happens in the ribosome. The connected amino acids are the peptides, which then get connected and properly bent into shape in the endoplasmic reticulum (where the Anavex sigma-1 receptor agonists have their function).
Now, back to Anavex 2-73. It does none of this, per se. Therefore, it is not “gene therapy.”
But in most cases (even better than gene therapy), it simply (well, rather “complicatedly”) causes all of the described processes to occur normally; particularly proper protein folding. Good enzymes are then produced. The cell must necessarily function normally.
Gene therapy is controversial. Messing with, changing DNA and genes, has a host of ethical issues. CRISPR-based gene therapies fall under a pile of regulations, restrictions, and prohibitions (as with the Chinese researcher who performed CRISPR technology on an in utero human fetus. He got fired.)
Anavex will encounter none of that. It doesn’t change genes. It facilitates their proper, healthful functions. In the infrequent cases of genetic diseases (as with Rett syndrome), Anavex 2-73 will not create a normal, healthful genotype. The little girls will continue have malfunctioning genes. But Anavex 2-73 promotes normal non-genetic functions that can suppress the untoward outcomes of the bad genes (as demonstrated in Rett-type mice; and soon enough, in real humans).
Anavex therapies will not be complicated or compromised by the restrictions and prohibitions of regulated gene therapy.
Probably Works; But Is Unworkable
Yes, some really fine therapeutic outcomes. Mental health of Alzheimer's patients wonderfully improved.
But, it was accomplished not with a drug but by an extremely detailed and complicated health "protocol." Simply, the therapists treated just a zillion health problems, and cognition improved.
Would (or could) you administer to Aunt Matilda all of the following when she started for forget stuff?
Here's stuff done and taken:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221920/#!po=34.0909
Optimize diet: minimize simple CHO, minimize inflammation.
Patients given choice of several low glycemic, low inflammatory, low grain diets.
Minimize inflammation, minimize insulin resistance.
Enhance autophagy, ketogenesis
Fast 12 hr each night, including 3 hr prior to bedtime.
Reduce insulin levels, reduce Aß.
Reduce stress; Personalized—yoga or meditation or music, etc.
Reduction of cortisol, CRF, stress axis.
Optimize sleep; 8 hr sleep per night; melatonin 0.5mg po qhs; Trp 500mg po 3x/wk if awakening. Exclude sleep apnea.
Exercise; 30-60' per day, 4-6 days/wk
Brain stimulation
Homocysteine <7
Me-B12, MTHF, P5P; TMG if necessary
[40]
Serum B12 >500
Me-B12
[41]
CRP <1.0; A/G >1.5
Anti-inflammatory diet; curcumin; DHA/EPA; optimize hygiene
Critical role of inflammation in AD
Fasting insulin <7; HgbA1c <5.5
Diet as above
Type II diabetes-AD relationship
Hormone balance
Optimize fT3, fT4, E2, T, progesterone, pregnenolone, cortisol
[5, 42]
GI health
Repair if needed; prebiotics and probiotics
Avoid inflammation, autoimmunity
Reduction of A-beta
Curcumin, Ashwagandha
43-45
Cognitive enhancement
Bacopa monniera, MgT
[46, 47]
25OH-D3 = 50-100ng/ml
Vitamins D3, K2
[48]
Increase NGF
H. erinaceus or ALCAR
[49, 50]
Provide synaptic structural components
Citicoline, DHA
[51].
Optimize antioxidants
Mixed tocopherols and tocotrienols, Se, blueberries, NAC, ascorbate, a-lipoic acid
[52]
Optimize Zn:fCu ratio
Depends on values obtained
[53]
Ensure nocturnal oxygenation
Exclude or treat sleep apnea
[54]
Optimize mitochondrial function
CoQ or ubiquinol, a-lipoic acid, PQQ, NAC, ALCAR, Se, Zn, resveratrol, ascorbate, thiamine
[55]
Increase focus
Pantothenic acid
Acetylcholine synthesis requirement
Increase SirT1 function
Resveratrol
[32]
Exclude heavy metal toxicity
Evaluate Hg, Pb, Cd; chelate if indicated
CNS effects of heavy metals
MCT effects
Coconut oil or Axona
Seminal Findings in the Anavex 3-71 Rat Study
I’ve copied what I believe are the four most important headline findings in the referenced paper, where Anavex 3-71 was administered to neurologically-diseased rats (merely in their drinking water; no injections, not intravenous).
https://anavex.com/wp-content/uploads/170330_ADPD-Vienna_HH-update.pdf
Make of these statements in the paper what you will:
1. AF710B [Anavex 3-71] fully reverts the cognitive deficit in aged McGill tg rats
Is there any existing drug that safely, persistently restores full cognition?
2. AF710B [Anavex 3-71] reduces AD-Iike amyloid pathology in McGill tg rats
Amyloid pathology is the main, pathologic feature of Alzheimer’s disease.
3. AF710B [Anavex 3-71] reduces inflammation in McGill tg rats
Inflammation is a root cause or severe complication of a majority of human diseases.
4. AF710B [Anavex 3-71] has synaptogenic properties
Ability to create or restore functioning nerve junctions (“synaptogenesis”) fixes a host of central nervous system diseases and dysfunctions.
“Yea, but thems was rats. We’s people. Don’t mean nothin!”
Ok, then. Let’s see what happens with Anavex 3-71 in real humans.
Anavex Life Sciences Corp has indicated they want to go that route, with people suffering from frontotemporal dementia (FTD). With the exception of amyloid pathology, FTD has all of the above (instead, it has tau pathology; which Anavex 3-71 may also remediate or prevent).