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The GABA problem.
Have you tried GABA supplements? [for hereditary spastic paraplegia]
Ah, blarcamesine has already been tested.
Thank you very much for this information, showing that early tests of blarcamesine (Anavex 2-73) have already been conducted on ALS animal models, successfully.
My conjecture is now a bit more firm. If I had ALS I'd be petitioning an ALS support association to encourage and underwrite human trials. But I have a different CNS disease, hereditary spastic paraplegia (HSP), making my legs stiff. Have to use a walker to amble about.
In that regard (HSP) I noted that the girls with Rett, in the first safety and tolerability trials of blarcamesine, showed that one outcome of blarcamesine therapy (even at low doses) was the markedly increased production of GABA, gamma-aminobutyric acid. GABA is deficient in the long motor neurons that control the muscles in my legs, allowing the nerves to continually fire; causing the spasticity. I'm so eager to participate in a clinical trial of blarcamesine for those of us with HSP. I'm certain that it will be therapeutic.
But before I petition the HSP support group, I'll wait for the results from the full Rett clinical trial. Those results will reveal the improved GABA factor. Everyone who understands the GABA-deficient pathology of HSP will instantly desire to start taking or allow blarcamesine. HSP is one of a number of hidden rare diseases for which blarcamesine will be profoundly therapeutic.
A distant but viable conjecture—ALS.
Ok, this is entirely conjectural; should not be a factor in considering the holding or purchase of AVXL shares. But most science begins with well-formed conjectures, which are then tested. What I describe below may, someday, be tested, with blarcamesine or another Anavex sigma-1 receptor activator.
Just read a research report that showed that the accumulation of specific waste or toxic proteins in the axons of nerve cells with amyotrophic lateral sclerosis (ALS) cause the disease symptoms. The paper claimed, “Clearance of axonal TDP-43 or dissociation of G3BP1 condensates restored local translation and resolved TDP-43-derived toxicity in both axons and NMJs. ... Clearance of axonal TDP-43 or dissociation of G3BP1 condensates restored local translation and resolved TDP-43-derived toxicity in both axons and NMJs.”
https://pubmed.ncbi.nlm.nih.gov/34824257/
Simply, if nerve cells can clear, remove the toxic proteins, the ALS (“ Lou Gehrig's Disease”) is resolved; a cure, dare I say.
Might it be that for those of us who do not have Lou Gehrig’s disease our nerves normally and continually clear away the toxic proteins? With this normal autophagy our nerves work properly. But, for some reason (genetic, chemically-induced, etc.), this normal autophagy fails in the neurons of those with ALS.
Might ALS be caused by a specific failure of normal autophagy? Moreover, might blarcamesine’s ability to restore autophagic processes in diseased cells be a treatment or cure for the disease?
That conjecture can’t be known until a lot of detailed, precise work is done. I note that there are mice that are animal models of amyotrophic lateral sclerosis (ALS). Won’t be inordinately expensive to test various dosages and treatment regimens of blarcamesine on them, to see if the diseased mice respond in any positive way. If they do, human trials would be next.
Again, the strength (not magic) of blarcamesine centers on its unique ability to favorably activate the sigma-1 receptor protein’s ability to modulate autophagy, thereby restoring healthful, normal homeostasis within the diseased neuron.
Once again, disrupted autophagy causes Alzheimer’s.
These results suggest, but do not conclusively demonstrate, that lower autophagic flux may be strongly associated with loss of function in AD brains.
Anavex nonsense; or science?
And there's a lot of nonsense out there that can mislead inexperienced investors and reckless speculators. Be careful.
Thanks, everyone. A great collective effort.
The information presented on this board is pretty phenomenal
Especially the scientific analysis, which is way better than most Wall Street analysts.
Side effects (from previous URL)
Here is a listing of side effects of dextromethorphan:
See your doctor as soon as possible if any of the following side effects occur while taking dextromethorphan:
Symptoms of overdose
Blurred vision
confusion
difficulty in urination
drowsiness or dizziness
nausea or vomiting (severe)
shakiness and unsteady walk
slowed breathing
unusual excitement, nervousness, restlessness, or irritability (severe)
Side effects not requiring immediate medical attention:
Some side effects of dextromethorphan may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
Less common or rare
Confusion
constipation
dizziness (mild)
drowsiness (mild)
headache
nausea or vomiting
stomach pain
Side effects.
Dextromethorphan is used for sleep problems. But given its side effects blarcamesine (which has very few and are mild and transient) will beat it.
https://www.drugs.com/sfx/dextromethorphan-side-effects.html
A prescription drug; and for sleep.
It will be quite a while before 2-73 becomes over the counter or available at that low price.
Then, beyond Alzheimer’s.
Yearly price for Blarcamesine treatment for Alzheimer's disease $3652.50
How blarcamesine gets approved is yet unknown.
Not sure why you would go down this road at this point. [Questioning the nefarious disqualification of blarcamesine by the FDA.]
Complications to the North, and Down Under.
What happens if the FDA fails to approve blarcamesine, after statistically significant data from any of the three clinical trials appear, showing both safety and efficacy?
Well, of course, because the professionals at the FDA are that, medical professionals, we can be assured that their decisions have been and will be based solely on sound, statistically significant clinical data (as in the manner of Biogen’s Aduhelm (cough)). We can be assured, pecuniary (money-making) factors won’t play any significant roles in drug approvals or therapeutic usages.
However, if nefarious, extraneous monetary factors somehow work their ways into the FDA’s disapproval of blarcamesine (Who could imagine?) and the drug fails to be allowed on American pharmacy shelves, the matter will not be domestically resolved.
Prescription drugs are sold in most of the world’s countries; not just the US. Will the Australians’ FDA, their Therapeutic Goods Administration, also be controlled or manipulated by Big Pharma stakeholders and likewise nix any use of blarcamesine Down Under — after the profoundly safe and favorable clinical results appear?
Might Australian bureaucrats punch the numbers of the costs of caring for ever larger numbers of Alzheimer’s and Parkinson’s patients each year, plugging in the tax-dollar savings that blarcamesine would annually and continually yield?
As powerfully brilliant and supremely knowledgeable as the FDA pooh-bahs are, even after being “taken to lunch” by Big Pharma lobbyists, they don’t control what drugs are allowed on the shelves of drugstores in other countries. Like the Aussies, our Canadian friends might well “interpret” the Anavex clinical trials data “differently.”
How will things play out when people with severe CNS diseases, in other countries, gain either disease prophylaxis or resolution, while Americans continue to suffer the lethal outcomes of the existing FDA-approved CNS drugs? Aussies or Canadians get substantial relief from Parkinson’s and Alzheimer’s. Americans don’t. How might all of that play out, politically, in the US?
“Well, as President of the US I have the greatest confidence in my experts at the FDA. They have the right information, have made the right decisions. I rely on what they say. They know best.”
Sure.
MOA Validations
I contend that in addition to the side effects differentiation of Anavex over Acadia, a powerful driver of the Anavex drug, first for Rett, then for the other CNS indications being targeted (being tested in clinical trials) will be blarcamesine's mechanism of actions (MOA).
If the Acadia drug gains approval for the treatment of Rett syndrome, will that approval tend to validate any other Acadia drugs or indications? Is the MOA of the Acadia drug applicable by extension to any other diseases? I see no evidence of such.
But when blarcamesine (Anavex 2-73) gains FDA approval for Rett therapy, its unique MOA (propitious activation of the sigma-1 receptor protein) will be recognized and clinically demonstrated. With that, it will be understood how it then, by the same MOA, can be therapeutic for other CNS diseases.
For both drugs, validation of the MOA will be important. For Anavex, it will validate potential therapies for other CNS diseases. Two of those are in clinical trial, Parkinson's disease dementia, and Alzheimer's. With the safety and therapeutic success against Rett syndrome, clinical successes demonstrated in the other two trials will be ever more sound. Approval for them should be forthcoming.
We’ll be taxed for Aduhelm
Medicare Part B, which covers services like doctors office visits, will increase by $21.60, from $148.50 in 2021 to $170.10 in 2022. Officials said that is one of the largest increases in recent years.
About half of that increase is due to contingency planning to make sure the program has enough money to pay for Aduhelm if Medicare decides to cover it.
https://thehill.com/policy/healthcare/584283-sanders-urges-biden-to-delay-medicare-premium-increase
Anavex and Autism
The autism rate among 8-year-old children in the United States is one in 44 and one in 35 in New Jersey, according to a Centers for Disease Control and Prevention (CDC) report that included researchers at Rutgers New Jersey Medical School.
More work showing sigma-1 receptor disease involvement.
A new paper in the Journal of Biological Chemistry describes detailed work characterizing the deep biochemistry of the sigma-1 receptor protein:
https://www.jbc.org/article/S0021-9258(21)01105-4/fulltext
It's now an error to presume that sigma-1 receptor biochemistry is either mysterious, difficult to discover, or inconsequential. A few years ago, those perspectives would have been valid. No longer. The central roles of the sigma-1 receptor protein, in modulating and facilitating a diversity of cellular processes are becoming ever more apparent.
An author of the paper, in a separate article stated the following: https://www.eurekalert.org/news-releases/936633
Prof. Lederkremer is optimistic about the new findings: “Having deciphered a crucial mechanism in the receptor's function, we have no doubt that our new findings can affect therapeutic approaches based on S1R, and hopefully alleviate the suffering of neurodegenerative patients, especially those with ALS.
I'm up, too.
My "dead" money is up 400%. I regret that it only has one life to give for my bank account.
I was wrong.
That's not how ALS is "generally understood". You're confusing Amytrophic Lateral Sclerosis with Multiple Sclerosis or MS.
Well, not an Anavex matter.
One minor correction, SA4503, cutamesine, is not an Anavex compound, but it has been shown to be a sigma 1 receptor agonist.
An Anavex molecule for ALS.
-dated Pr yet ALS still on the drawing board--what say you for possibilities ??
Blarcamesine induction of pan-viral destruction.
With a thousand trial participants (give or take, not sure of the exact number),currently taking A2-73 worldwide, have any contracted Covid while taking the drug?
In drug development, observations don’t count.
If our drug does very well in subset of patients shouldnt it be obvious to clinicians? And dont remarkable fin[din]gs warrant early intervention by fda before trial termination?
Actual Anavex science will be secondary.
The good news is, [Anavex] science will lead now for a long time period of evolution....
Looking out to an Anavex future.
Thanks for those corrections. I didn’t closely determine the Microsoft share price over the years. But, anyone who took an early equity position (and held it), today has some very handsome value gains. Back then (early ‘90s), had I known, I’da scraped up $1000 and bought in. But, I didn’t. Nothing for me to talk about (regarding Microsoft).
The question here is whether or not Anavex will yield big gains in the coming years. I knew very little about computers, computing, or potential share prices for the new companies leading the new technologies. Not so with Anavex. I’m an accomplished, knowledgeable biologist; can understand the arcane complexities of both general cell biology (taught it to talented students in a very select college-preparatory program; where my students went on to gain science scholarships and earn advanced degrees), and the particular, unique medical biology of the Anavex molecules. With those understandings, I’m confident in the eventual success of my modest Anavex investment.
If Anavex gains regulatory approval to sell blarcamesine to treat but any one of the three CNS diseases currently targeted, Rett syndrome, Parkinson’s disease dementia, or (the real biggie) Alzheimer’s disease, the AVXL share price will increase by an order of magnitude (10X) or more.
But there is the real possibility, pending eventual clinical-trial affirmation, that the Anavex molecules will be able to treat or prevent any number of other neurodegenerative or geriatric (age-related) diseases. Of particular impact will be the discovery that blarcamesine (or Anavex 3-71) produces profound prophylactic, disease-prevention outcomes. As Dr. Missling, Anavex CEO has already mentioned, there is the possibility that someday mass numbers of people will take a tablet of an Anavex drug each day, to ward off untoward aging or geriatric diseases. When everyone at the age of, say, forty needs to start popping an Anavex pill with breakfast each day, one or two more zeros will be needed to indicate the AVXL share price.
Then, finally, there is the distinct possibility that an Anavex molecule, by its propitious modulation of chromatin functions in chromosomes would markedly reduce mutations in germ cells (ova and spermatozoa). Were that the case, males would take the Anavex drug before fathering children. Women, because the genetics of ova are determined at a very early age, even before birth, would have to take the drug during their entire lives; to minimize genetic defects in first her ova, then in the children those would produce.
All of this will need to be properly determined and demonstrated. Many clinical trials on the Anavex horizon.
And I remember Microsoft, Apple, etc.
We will be more well known than J&J. In every household.
Here's what Schwab says.
As suggested by Tom, I clicked on the "B" icon on my Schwab account, and got this:
If RCB (Regulatory Circuit Breaker) displays next to the Action field in the trade tab, the Reg SHO regulatory circuit breaker is in effect for the stock. The Securities and Exchange Commission (SEC) has adopted amendments to Regulation SHO (Reg SHO). Under Rule 201, the SEC has established a short sale-related circuit breaker that, if triggered, will impose a restriction on when and/or at what price a security may be sold short.
The short sale-related circuit breaker will be triggered for a security when its price declines by 10% or more from the prior day’s closing value within normal market hours. The regulatory circuit breaker will then remain in effect for the remainder of the day, and at a minimum, throughout the next day’s trading session. The circuit breaker will be triggered during the regular session only. Once triggered, the price test will apply at all times when the national best bid is disseminated through the end of the next trading day.
When the regulatory circuit breaker rule is in force, short sale orders will continue to be accepted. However, marketable limit orders and market orders to sell short may be delayed and executed at a significantly lower price than the bid at the time the order was placed.
Schwab says trading halted.
Yep, checked my Schwab account. At 5:25 EST said trading halted for AVXL.
I'm keeping my moderate AVXL position; don't intend to sell and shares for a good number of years. But like everyone else, will be interested to learn who, why, and/or how trading was terminated.
Anyone want to fill us in on this? Who has the authority to stop trading? For what purpose? Then, when and how does trading resume? Who makes that decision?
Is this weird, or what?
COVID-19, autophagy, and the aging process.
The discovery (in the previously referenced study; paper) that the SARS-CoV-2 virus is able to disrupt normal autophagy processes in cells, thereby disrupting the cells’ ability to consume or destroy those viruses might help explain why COVID-19 in children is seldom severe, whereas in the elderly it so often is. With aging, many processes diminish. Diminished autophagy is a recognized feature of aging:
The decrease in autophagic activity observed in almost all cells and tissues as organisms age was proposed to contribute to different aspects of the aging phenotype and to the aggravation of detrimental age-related diseases.
Blarcamesine could stop COVID-19? A mechanism?
Now, a team headed by Vojo Deretic, PhD, distinguished professor and director of The University of New Mexico’s Autophagy, Inflammation & Metabolism (AIM) Center of Biomedical Research Excellence, has mapped out key details of how autophagy functions in mammals – including humans.
And, in a startling finding, the researchers provide evidence showing that SARS-CoV-2 infection can disrupt the process.
Highlights
•
Mammalian autophagosomes are formed via fusion of cis-Golgi and endosomal membranes
•
This forms a prophagophore termed hybrid pre-autophagosomal structure (HyPAS)
•
HyPAS depends on SNARE STX17 and its interactors E-SYT2, SIGMAR1, and SERCA2
•
SARS-CoV-2 inhibits prophagophore formation by nsp6 targeting HyPAS apparatus
If Fragile X, Then Autism?
In this paper (co-authored by Dr. Randi J. Hagerman), Autism Symptoms in Fragile X Syndrome (https://pubmed.ncbi.nlm.nih.gov/28617074/), the first sentence of the abstract states, “Fragile X syndrome (FXS) is recognized as the most common genetic cause of intellectual disability and autism spectrum disorder (ASD).”
As the paper will describe, fragile X syndrome, in many cases, is connected to, or is a comorbidity of autism spectrum disorder.
Because the two disorders are closely related, might it turn out that individuals with other forms of autism will be helped with blarcamesine therapy? Dr. Hagerman has already spoken of her support of blarcamesine for fragile X (in the human clinical trials she is conducting).
If blarcamesine proves to be a useful, safe, efficacious therapy for most or all forms of autism, what might be the size of that market? What would be the social and economic implications for markedly reducing the numbers and severities of individuals suffering from autism?
Look it up. In a web search engine, query with this question: “Number of Autism Cases in the US.” Or, “Economic Impact of Autism.”
The results of the Anavex fragile X syndrome clinical trial should be illuminating; certainly for fragile X, but perhaps also for other autism forms.
Improved Biochemistries
Ain't this (statistically) just great:
"“We now have robust and concordant data that ADUHELM has effect on two core defining pathologies of Alzheimer’s disease, and substantial evidence of treatment correlation between changes in plasma p-tau181 and the slowing of disease progression,” said Alfred Sandrock, Jr., M.D., Ph.D., Head of Research and Development at Biogen."
But, can the people taking the drug now actually think better?
And, how long will those putatively improved biochemistries persist? A short or long term fix (if anything functional at all)?
Some meager (but 'precise') molecular data. Great. Now, let's learn of the actual functional, behavioral benefits (if any).
Who's gonna show those first for Alzheimer's? Anavex or Biogen?
Alzheimer’s Walks Next Year
This, and other similar public “walks” and demonstrations, prompted by an expanded, dare I say even desperate, search for a solution to the Alzheimer’s Problem, should not go unnoticed. We baby boomers are aging out, with millions of us facing the prospects of geriatric dementias, the most prominent of which is Alzheimer’s disease.
The stark reality of there being no useful, effective treatment or prevention of Alzheimer’s confronts modern society. Formerly, the affliction was reasonably rare; could be neglected. But, today, probably a majority of families have distant members suffering as either Alzheimer’s care givers or patients. Everyone with such arrangements has asked, “What can be done for Aunt Sally?” Nothing. She will suffer, then die.
The futility of treating or caring for an Alzheimer's patient (or relative) is evermore frustrated by the now-recognized failures of both Aricept and Aduhelm. Aricept, for a short or moderate period, only slows the lethal progression of the disease. Aduhelm is unbelievably expensive (health insurance may not pay for it), and it has very bad side effects, and yields very moderate symptomatic relief, which does not endure.
Simply, there are no treatment or prevention modalities for this horrible disease.
What, then, might happen when, next year, Anavex announces the very favorable results of their big Phase 3 Alzheimer’s clinical study? Will those people participating in Alzheimer’s marches merely blink their eyes and walk on? Or, will they take their concerns to both legislators and federal health agency officials? How soon would there be new Alzheimer’s marches, with signs and shouts: “We Want Blarcamesine!?”
When they appear, blarcamesine’s Alzheimer’s clinical data will change everything.
Feelings and Evidence.
Three shots on goal, if all three score, AVXL upside price is in the stratosphere! Me, liking our chances of 3 shots, 3 goals! Just got that feelin'
Globally, $95,000,000,000,000 investment dollars available for AVXLs.
SAVA is only a threat to its stockholders. It is no threat to AVXL.
Mice, poor sleep, and Alzheimer’s
Here’s a report on a new study of sleep deprivation in mice, associated with (or causing) amyloid wastes associated with the Alzheimer’s symptoms of the mice:
https://www.eurekalert.org/news-releases/933728
Of course, this is presently of no immediate importance to blarcamesine, when used as a treatment for Alzheimer’s in humans (as being presently tested in big, proper, placebo-controlled, fully blinded clinical trial). But blarcamesine has improved or restored normalized sleep in humans. Let’s let the trial data reveal if the drug’s facilitation of healthful sleep is but an additional factor in blarcamesine’s Alzheimer’s efficacies.
Ah, that's the term.
Great example, its like a biological cascading affect!
Binary? Or multifactorial?
Could there be a case where over expression of S1R function is as detrimental as "under-expression"?
Yes, blarcamesine stoops, strongly.
Thanks for that one falconer, The bird is in a dive picking up speed and it’s prey will not know what hit them....
Blarcamesine works way beyond sigma-1.
You might want to add that 2-73 is a muscaric receptor agonist in addition to being a Sigma-1 agonist.
Big hit with Rett. Homerun with PDD.
I am trying to understand which positive results, Rett or PDD OLE, has the most impact to AVXL stock price, sure both positive is the homerun outcome, thanks again.