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A Big Alzheimer’s Trial is Ongoing
Blarcamesine for Rett can be all in-house.
Who gets the first SIGMAR1 Award?
But more than the science.
Mothers of Rett daughters will speak.
The only things that count....
Not dots; only double-blind clinical trials.
But then for other conditions?
Testing for seizure prophylaxis.
Blarcamesine and The SOC.
Blarcamesine first in the UK? Or, Down Under?
Do a web search “sleep deprivation costs, frequencies.”
Negating details not presented.
Numbers now, or in years out?
Those 4-digit AVXL share-price projections, several years out, match the ones my spreadsheet calculations present. I make the same presumptions; that blarcamesine will be approved as an Alzheimer’s therapy, and that several million will then take the drug, at the projected $10/day expense.
Of course, the numbers may be off by 50% or more. Alzheimer’s is an un-treatable malady in the rest of the Western world. The European market should match the American. The numbers very reasonably could then be doubled.
But that will be only the Alzheimer’s chapter in the Anavex story. Once hundreds of thousands are taking blarcamesine it will be incidentally discovered that not only are their targeted pathologies being resolved by the drug, but they incidentally are far less subject to other diseases (such as viral infections such a COVID, colds, flues, etc.).
After a few years (Should be but a few months, but the FDA is, to use an inept phrase, is “always cautious.” Never again any thalidomides.) very high chance blarcamesine is allowed to be used as a generalized geriatric prophylactic. Take the stuff to prevent or delay the onset of a host of geriatric diseases and conditions.
At $10 a day, that’s an annual drug cost of $3650. If blarcamesine works as a late-adult generalized disease prophylactic, would that annual cost offset the eventual healthcare costs of the prevented diseases in old people? Almost surely.
Not included in any of these projections are the yet-to-be-confirmed efficacies of Anavex 3-71. Every bit of evidence shows that it is likely to eclipse blarcamesine in every regard, yielding even better and more diverse disease preventing and treatment outcomes. In the end (five years from now) Anavex 3-71 will likely supplant blarcamesine, yielding both greater treatment outcomes and revenue streams.
In over a half-decade I’ve accumulated my modest AVXL holding as a long-term investment, not a trading vehicle. Most likely I’ll never sell a share. The holding will remain in my estate, to the benefit of my family, church, and community benefactors. My wife and I, in our remaining years (free of geriatric dementias of any sort) will live very comfortably on Anavex dividends. I’m a biologist, can comprehend the unique cellular biochemistry of the Anavex molecules, and note cogently that they are both safe and efficacious. Not a shred of evidence in either murines (lab test rodents) or in any humans in any of the several trials that blarcamesine or Anavex 3-71 produce any clinical data indicating that they can’t or won’t be approved. I won’t go into them here, but I’ve previously laid out many of the potential problems with neuroactive drugs. The Anavex molecules have none of them.
I sleep well knowing that I must wait until the Parkinson’s disease dementia and Alzheimer’s trial results appear. The Anavex naysayers will strive to tell why, once again CEO Missling and the company’s drug have failed and it will not be approved. Same quibbling, whining chatter as now. But to no avail. I can wait until 2023 or 2024. Missling, blarcamesine, and Anavex will then be vindicated. All will be well; especially for the millions benefitting from blarcamesine treatments.
Any reasonable shareprice conjectures?
ALPPine share prices presently continue to slide sideways. I’m trying to estimate the potential value of my ALPP holding at the end of 2022. Any reasonable, conjectured share price ranges in a year? I bought a bunch just before the NASDAQ uplisting, anticipating the envisioned share price rise. Hasn’t yet happened. Thoughts? (Not going to sell my holding; will wait no matter what happens.)
What will parents and caregivers decide?
Well, I’m certain that parents and caregivers of women with Rett syndrome will see right through all of the positive things disclosed in the trial results. Instead of focusing on how blarcamesine has been clinically shown to significantly treat and relieve the symptoms of Rett syndrome in older, post-pediatric subjects, they’ve read the so important info here, showing that Anavex "adjusted things” during the trial, so their people with Rett shouldn’t take blarcamesine. The clinical results were really good. On the basis of just those life would be so much better for the women with Rett.
But, nope. Can’t or won’t be. Certain alleged “adjustments” during the clinical trial entirely negate, disqualify both the positive safety and efficacy outcomes. More than we incidental AVXL shareholders the parents of women with Rett know what their girls should be taking. They aren’t going to stand for any effective, safe drug that had some sorts of “adjustments” happen during the clinical trial. Not gonna have any of that, for sure.
Or....
Another Blarcamesine Success, in Humans
Anavex/blarcamesine naysayers really have to stretch to find facts that show that the drug is either unsafe or ineffective. Have we seen any of those failures laid out today? The clinical outcomes from the completed clinical trial in humans, with advanced cases of Rett syndrome, are all positive. Not a single datum (compared to placebo) was negative. All clinical outcomes are statistically significant.
https://www.anavex.com/_files/ugd/79bcf7_ca78f07355544ad794235b95a121f8d0.pdf
This continues the universally positive findings in every clinical study of blarcamesine; first in trans-genic (human-diseased) murines (lab rodents), now in a placebo-controlled Phase 3 clinical study in diseased humans. This will continue with the Parkinson's disease dementia and Alzheimer's trials. For blarcamesine, the FDA will have it.
Facts and experts of no consideration.
Blind? Nope. We see beyond the horizon.
Anavex MOA WORKS. PDD and Alzheimer's Next!
Murine Data Confirmed in Humans
Whadya know? The murine trials of blarcamesine successes against Rett were entirely predictive of the drug in humans with the disease.
Wanta now contend that this won't be the case in both Parkinson's disease dementia and Alzheimer's? Ha.
When I get a few more discretionary dollars, I'll be expanding my AVXL holding.
Not A "Purchase? How So?
Wasn’t A Whim Purchase
Eventual Discovery in Humans of Antiviral Efficacy
Ok, very likely the SARS-CoV-2 virus, by natural selection, will devolve to a persisting pathogen, in the manner of colds and flues. No evidence whatsoever that any of the current "vaccines" will be able to extinguish the virus from any human population.
So, in two or three years from now, when blarcamesine is the SOC (standard of care) therapy for at least three morbidities, Rett syndrome, Parkinson's disease dementia, and Alzheimer's, it may be inadvertently discovered that those taking the drug don't suffer from SARS-CoV-2 infections themselves, or even other common viruses such as those of influenza and common colds.
First, is there any chance for this to be the case? Well, if activation by blarcamesine of the sigma-1 receptor protein facilitates (as it does) a diversity of "downstream" cellular maintenance functions, restored, optimized autophagy within cells will facilitate the destruction or expulsion of virions, virus particles. If viruses can't get inside cells, they can't replicate. They are a pathogenic dead end; merely an extraneous packet of non-functioning genetic nucleotides (DNA or RNA).
As Dr. Missling's long-ago statement "like an iceberg" might indicate, when tangentially in reference to the potentials of the Anavex sigma-1 receptor agonists, I'm certain that Anavex insiders know far more about their drugs than they are presently telling. It's not at all expensive or difficult to infect various common lab test animals (murines, rats and mice; Ceanorhabitis elegans, a common lab roundworm used for genetics, aging, and pathogen research) and see how treatments with Anavex molecules affect various microbial infections.
Restoration of optimized cell functions by blarcamesine might well yield profound antimicrobial outcomes. Not just time, but the reduced incidences of viral infections in people taking blarcamesine will tell.
Of course, categorically that fits inside the blarcamesine prophylaxis thesis; that dosing with blarcamesine will prevent the onset of various diseases, such as the targeted CNS diseases, along with the debilities of normal advanced aging.
Right now, we're still in the early chapters of the eventually gigantic Anavex story book. It won't be just Rett syndrome....
Blarcamesine "Now" for Rett
Rett, only?
Shall we quibble over dosages, or efficacies?
Granted, Anavex 3-71 dosages in current human trials are orders of magnitude greater than in the therapeutically successful treatment of human Alzheimer's in lab rats.
But the more important matter is that the molecule, in such minute concentrations (micrograms, not milligrams) worked. It didn't just halt the progression of the cognition decline Alzheimer's, it reversed it. Moreover, this restored cognition was retained after the drug was no longer administered. The positive therapeutic outcome persisted after the drug was deleted.
Again, here's the text from the paper, with my typefacing:
Successful Anavex 3-71 Dosage Against Murine Alzheimer’s
In this study, of transgenic (Tg) rats with human Alzheimer’s genes (and disease), Anavex 3-71 (AF710B) was dosed at a rate of 10 µg/kg per day, orally administered. At that tiny dose Anavex 3-71 produced reversion of cognitive deficits of the disease --- a therapeutic success.
https://www.researchgate.net/publication/322142767_AF710B_an_M1sigma-1_receptor_agonist_with_long-lasting_disease-modifying_properties_in_a_transgenic_rat_model_of_Alzheimer's_disease
Here’s an excerpt:
After Blarcamesine, Anavex 3-71 Will Be Big(ger)
Understandably, the focus on Anavex Life Sciences Corp is centered on Anavex 2-73, blarcamesine; presently in three definitive clinical trials, for Rett syndrome, Parkinson's disease dementia (PDD), and Alzheimer's. The immediate future of Anavex depends on the clinical safety and efficacy of blarcamesine to treat at least one of these otherwise recalcitrant central nervous system (CNS) diseases. A large body of previous postings indicate the evidence why the drug is so very likely to exhibit favorable clinical outcomes.
But presently very little attention is being paid to Anavex's other new drug candidate, Anavex 3-71. I'm not going to re-post any of them, but feel free to do a postings search on Anavex 3-71. Simply, it has an even greater therapeutic potential than blarcamesine. It works therapeutically in doses fractional to those of blarcamesine; with phenomenal therapeutic outcomes against a wider diversity of CNS and other disease categories.
With Rett syndrome results soon to appear for blarcamesine, it will be the headline drug from Anavex; then even more so with the PDD results. Finally, sometime in 2024 will be the big Alzheimer's results.
But watch. waiting actively in the wings is Anavex 3-71, waiting to take the CNS (and perhaps COVID-19) treatment stage, when that act opens next year. Anavex 3-71 may end up being Anavex's biggest drug and revenue generator. Time (and clinical results) will tell. The preclinical data from murines (lab rodents), like those previously from blarcamesine, are extremely favorable; against a much wider body of diseases; particularly by muscarinic receptor activation.
As a retail (private individual) holder of a moderate AVXL position (several thousand shares), I've perceived from my Anavex investment start, about five or six years ago, that this investment would take a lengthy period to pay off. On paper (well, on my spreadsheet) I have a very nice value appreciation of my AVXL position. But I've never sold a share (have taken no profits), and don't intend to for many years. Knowing to a reasonable degree the biochemical intricacies of the biochemistry of the Anavex molecules, I'm satisfied to patiently wait for Anavex to gain FDA approval to sell one of their drugs. In 2023, my spreadsheet cells indicating AVXL share prices will have to add another digit or two. In the Total Value cells (share price x number of shares), at least two digits will have to be added there, too.
A worthwhile wait.
Pretty Lively Cat
Today's price bounce, that attributed by the share pricing experts to a "dead cat," was pretty lively.
The AVXL cat didn't "bounce" today; it gained value right to the end, never falling, closing but a penny off the high of the day, which was in the last minutes of trading --- if any of this means anything for the future.
The real future for the AVXL share price will be determined by the quality of the clinical results for blarcamesine against a) Rett syndrome (soon), b) Parkinson's disease dementia (later in 2022), and finally, c) Alzheimer's, in the trial ending in late 2022 or in earlier 2023.
I chuckle, smirk, and yawn while reading the ever so-helpful prognostications on the near-term AVXL share prices. Postings will be rather different when trial results appear. Anavex naysayers will say their nayings; we Anavex enthusiasts will post our interpretations. All the while, the AVXL share price will ascend.
"TLD?"
Sleep, Night Darkness, and Alzheimer’s
As the referenced article on the relationship between deep sleep (absence thereof) and Alzheimer’s notes, one of the more important functions of sleep is to allow the brain to clear out wastes. Toxic wastes in brain tissues are implicated in virtually every explanation for the cause of Alzheimer’s.
https://www.nih.gov/news-events/nih-research-matters/how-sleep-clears-brain
For many years the metabolic activity of the brain during sleep was a puzzle. While the rest of an animal’s body (including human’s) metabolically rests during sleep, not so with the brain. During sleep, the entire body consumes about the same amount of energy as when awake. But the body does rest. At night, the brain consumes, uses a greater proportion of the body’s total energy.
What is the brain doing with that energy during sleep? Well, it helps arrange and store memories. But importantly, it uses much of the energy to clear chemical wastes from the brain and associated nerves. Hence, the connection between deficient or poor sleep with the eventual onset of Alzheimer’s.
But, in modern life, one significant environmental factor has greatly exacerbated the poor sleep/brain dysfunction problem — light.
Before modern lighting changed living patterns, beginning in the early parts of the last century, when electricity powered electrical lamps, after sundown each day the only light available in buildings, residences, was from oil lamps or candles. Good enough to read (however strenuously) a book. The mind’s eye, as it were, had to work a bit to see anything lit by a candle or oil lamp. Then, when it was time to retire, the lamp or candle was snuffed out. Until sunup, the natural, deep darkness of the night; during which the sleeping brain, very actively could both consolidate memories and clear away accumulated toxins. A good night’s rest, for mind and body.
But my hero, Thomas Alva Edison, with his electrical lamps and electrical generation and distribution systems, changed human lives. Light was everywhere, 24/7. The human brain was genetically and physiologically unprepared. Sleep patterns were compromised; shorter, and prefixed by long, bright light periods In the evening. Unnatural, altogether. But far more convenient.
Two major problems ensued; still not widely recognized or managed.
The first is the color of modern lighting. Bright and cheerful. In the language of color photography, modern lights are “cold,” are predominated by hues at the cold or blue end of the spectrum; in contrast to the “warm,” reddish hues of a candle flame.
The fact is this: the brain takes light color signals from eyes as the day wanes. Naturally, as the sun sets, the bluish, “cold” hues subside, the reddish, “warm” hues predominate. This signals to the brain that sleep will soon follow. With the warm-color cues in the evening, the brain starts producing melatonin, a hormone that induces and promotes sound sleep.
But, today, we stay up late, lit all the evening with cold bluish lights. We go to bed, flip off the light, and try to sleep. But the brain has had no signal to prepare for sleep. No period of warm, subtle, reddish light to turn on melatonin production. That can take some time; while we stare at the bedroom ceiling trying to get to sleep.
But that’s when the second severe problem sets in. Light, again. Yes, after you’ve closed your eyes, light; when you are trying to sleep.
Fact is, eyes are extremely sensitive to the presence of any slight amount of light; even with your eyes tightly closed. When you go to bed tonight, after all the lights are out, open your eyes, see if you can see anything. You will see, however dimly, everything. Almost no one sleeps in an entirely dark bedroom. There is vagrant light from a multitude of sources; a hall light, light streaming In from a street light; even the lighted panel of a radio. With your eyes closed they can detect all of these, and will continuously, through the night, send “we’ve got light in here” signals to the brain. The brain fails to go into its normal, ancestral deep-sleep waste-clearing status.
Until I had to be in the Cleveland Clinic for kidney surgery (kidney stones), I thought all of this was crazy. But during my night of post-surgical recovery, I couldn’t sleep. The nurse left my room door wide open to the long hall outside. The lights in my room were out, but light streaming in from the hall kept me awake. I asked the nurse, “Can you close that door, so I can sleep?”
“Sorry, not allowed. Have to keep it open so we can hear patients who might call for help. But I’ll fix it for you in just a minute.”
She walked in with a black night mask, which she told me to place over my eyes. I put the thing on, carefully aligned it so no light could sneak around the edges; and slept like a log.
When I got home, I bought an even better, more closely-fitting night mask; have been using one now for 7 years. My mind remains as sharp as ever.
Then, about three years ago, I read that I should also adjust my Windows computer to turn off the cold, bluish portions of my monitor’s color spectrum after about 7pm. Did that; sleep even better now. My brain in the evening detects that things are getting warmer, more reddish; that sleep will ensue. Now, I fall asleep within minutes at night — and remain soundly asleep all night, with my night mask keeping out all of the extraneous synthetic light.
Give those things a try. Adjust your computer monitor to automatically go to warm hues early in the evening. Then, purchase and use a well-fitting night mask during sleep. You’ll be astounded.
And the brain’s clearing of wastes at night might tide you over until blarcamesine becomes available in a few years.
Can it be....?
But efficacy yet to be “proven.”
No preclinical hints or evidence of problems.
Blarcamesine against ALS.
Gabapentin Not Effective For HSP
Two other CNS diseases blarcamesine will treat.
But, only trial outcomes count.
Mothers can tell.