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Thanks again Sokol. This post contains a trove of critical knowledge and facts (IMHO) which helps to link AVXL to the CNS diseases CORE solution.
The Mitochondria–Endoplasmic Reticulum Contacts and Their Critical Role in Aging and Age-Associated Diseases
Ornella Moltedo,1 Paolo Remondelli,2,* and Giuseppina Amodio2,*
Author information Article notes Copyright and License information Disclaimer
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Abstract
The recent discovery of interconnections between the endoplasmic reticulum (ER) membrane and those of almost all the cell compartments is providing novel perspectives for the understanding of the molecular events underlying cellular mechanisms in both physiological and pathological conditions. In particular, growing evidence strongly supports the idea that the molecular interactions occurring between ER and mitochondrial membranes, referred as the mitochondria (MT)–ER contacts (MERCs), may play a crucial role in aging and in the development of age-associated diseases. As emerged in the last decade, MERCs behave as signaling hubs composed by structural components that act as critical players in different age-associated disorders, such as neurodegenerative diseases and motor disorders, cancer, metabolic syndrome, as well as cardiovascular diseases. Age-associated disorders often derive from mitochondrial or ER dysfunction as consequences of oxidative stress, mitochondrial DNA mutations, accumulation of misfolded proteins, and defective organelle turnover. In this review, we discuss the recent advances associating MERCs to aging in the context of ER–MT crosstalk regulating redox signaling, ER-to MT lipid transfer, mitochondrial dynamics, and autophagy.
nlm.nih.gov
kevindenver
2 comments stand out: "The changing therapeutic landscape" and "There are really interesting small molecules directed at disease modification" that could refer to the adding the small molecule blarcamesine to the changing "drug development pipeline".
Thx Sokol.
So Many Dots, so little time.
Mitochondrial diseases can affect almost any part of the body, including the cells of the brain, nerves, muscles, kidneys, heart, liver, eyes, ears or pancreas.
Mitochondrial dysfunction occurs when the mitochondria don't work as well as they should due to another disease or condition. Many conditions can lead to secondary mitochondrial dysfunction and affect other diseases, including:
- [Alzheimer's disease](https://my.clevelandclinic.org/health/diseases/9164-alzheimers-disease-an-overview).
- [Muscular dystrophy](https://my.clevelandclinic.org/health/diseases/14128-muscular-dystrophy).
- [Lou Gehrig's disease](https://my.clevelandclinic.org/health/diseases/16729-amyotrophic-lateral-sclerosis-als).
- [Diabetes](https://my.clevelandclinic.org/health/diseases/7104-diabetes-mellitus-an-overview).
- [Cancer](https://my.clevelandclinic.org/health/diseases/12194-cancer-overview).
ShowImage.ashx
Mitochondrial Diseases: Causes, Symptoms, Diagnosis & Treatment
my.clevelandclinic.org
I hear this guy saying that the FDA "silver bullet" Amyloid plaque thesis is finally dead (note many recent FDA fails) and that CNS diseases (like AD) will use AVXL ("00 Buckshot-mixed loads).
"The changing therapeutic landscape" and "There are really interesting small molecules directed at disease modification"
jonjones325
Since almost 4 months have passes, I think we can say that a bad news surprise is off the table.
That only leaves good news. How good is the question? Even if we need to do another Alz trial with "real" PMA - that is not bad news per se since judging by our share price no one really expects any type of approval. We may even go up on "a real pivotal" trial news.
Rett is coming and all indications tell us to be confident. At least the stats will be in order.
With all our IP and the rest of the trials that are "soon" to be initiated, it's difficult to see how we are not undervalued right now.
Standing by for some kind of WW CNS disease partnership news or possibly some kind of joint venture(s) to include big AI and BP collaborative plans. This kind of silence can only be kept at certain levels for so long. Even George has been silent. (all IMO)
crescentmotor...
The stock market is very vulnerable.
then the real beatings will be administered
plexrec
-he shares "unpublished data" with an audience down under and we don't know what that may be !!!
Blarcasamine
Hopefully some of the whales taking advantage of the low stock price this morning down about 3%.
After reading this well written piece I understand better why AD is where it is. Like me, many here may have spent long days in conference rooms w/long debate tables lined by topic-subject experts . "We get it", not everyone sees the argument with the same (eyes, wisdom, reasoning, background, education and precision ....and...they never will).
In fact I bet many here have witnessed fine-line long debates that proved absolutely nothing except two individuals do not like/understand each others point of view, and they never will. Can we just move on? In some cases these hopeless debates in trivia are relegated to resolution by some use of statistical reasoning, which typically resolves nothing. (sound FDA -like familiar to anyone?).
This is where a favorite old Irish expression of problem solving is applied ...,"Unconstrained by knowledge, we moved on."
Not a surprising conclusion. In fact, it explains a lot. Why else would people like Dr.M. avoid the established system when he is holding a full CNS house. IMO, b/c he knew the game is rigged/stacked/corrupt. This is also consistent w/last few years of FDA open corruption and dysfunction.
Maybe now we can all move on.
https://unbekoming.substack.com/p/peer-review
These magazines are real businesses, so necessarily sensitive to advertising revenues and "reprints" granted by Big Pharma!
And as if this were not reason enough to be suspicious, you should know that the main shareholders of Elsevier are also the main shareholders... of Big Pharma!
For example, BlackRock, to name but one, is the number 1 shareholder of RELX Group, and one of the top 10 shareholders of... Pfizer.
It's even worse than that, because the number 1 shareholder of Pfizer is Vanguard Group... who is himself the main shareholder of BlackRock!
In short, these are the same players (and probably the same people) who own the leading medical journals AND the major pharmaceutical multinationals.
- Dr. AS Relman, professor of medicine at Harvard:
“The medical profession is being bought off by the drug and vaccine industry, not only at the level of medical practice but also at the level of teaching and research. Academic institutions in this country (USA) have indulged in becoming paid agents of the pharmaceutical industry. I find that hideous.”
- Dr M Angell, physician, former editor of the New England Journal of Medicine:
"It is simply no longer possible to believe the essential clinical research that is published, or to rely on the judgment of reference doctors or to authoritative medical guidelines. I take no pleasure in making this observation, which I came to slowly and reluctantly over two decades as editor of the New England Journal of Medicine.”
- Dr R Horton, editor of The Lancet:
“A scandalous number of published studies are unreliable at best, when they are not completely misleading, in addition to fraudulent. Much of the scientific literature, perhaps half, may simply be untrue. Afflicted by studies with small sample sizes, tiny effects, invalid exploratory analyses, and flagrant conflicts of interest, together with an obsession for pursuing fashionable trends of dubious importance, science has taken a turn towards darkness.”
Thanks falconer.
Yes, not only is the Anavex "stuff" working, but Missling and company know both that it does and how it works. Anavex now knows the precise molecular details of exactly what happens in diseased neurons when their sigma-1 receptor ligands activate that crucial molecule.
Rett Syndrome Association of Australia presented at the 2nd Childhood Dementia Symposium in Sydney and Dr Missling presented on the possible usage of Anavex therapeutics for childhood dementia.
HMB2010
Interesting correlation. Was not aware there was childhood dementia. A quick Google of the term enlightened me. Thank you for sharing!
jonjones325
You may be on to something.
https://www.dementia.org.au/about-dementia/types-of-dementia/childhood-dementia
Missling is all about learning about what 2-73 can do. Looking at the wide range of symptoms associated with childhood dementia, 2-73 would be a good fit.
The larger picture could be an umbrella type drug that can alleviate a multitude of childhood rare disease ailments. Endgame?
jonjones325
You can zoom any meeting, even court appearances. Missling chose to go down in person because whatever it was, he felt it was important enough for him to physically be there.
The old Cowboy expression comes to mind. "Ride low in the saddle and stay off the horizon".
traderpete
The Market loves volatility, pump it up and down and rake in the cash. Get free shares, get rid of retail, etc. They want to add as much heat as possible so they can manipulate things even more.
Some things that could happen with, proving it works, before a deal can be worked out in a sane fashion.
1. The price could skyrocket, possibly enticing enough share holders to force a sale, well below where it could be in a year or two.
Imagine that you are a passenger on a bus. You bought your ticket based on the sign on the front of the bus . (CNS disease AD, PPD, Dementia, ...see posted plans/schedule), so you find a seat and look out the window at all the helpless pedestrians staring in wonder as their lives go by. You may take some comfort in the thought that (at least you are ON the bus), you can get off anytime you want.
There seems to be a lot of angst and turnover but the driver appears not to be distracted. He acts like he has enough time and money to finish his plan (traffic-accidents not with standing). He suggests from time to time he is getting close to the final stop but then he just drives right past the clinic. Passengers start yelling about the schedule, to which the driver simply asks..."Do you want to get OFF??" . If Yes, he stops and then....bye, bye.
Bus is getting crowded again. We each have to decide , either get off, sit down and STXU, move around and continuously make life tougher than it has to be or have some confidence you have continued to make the good-right choices. BTW, life is short, then you die.
Please send link to this doc...no joy looking so far...TIA
Wolfof
History has taught us that being first to market is not always best.
Being second to market with a drug that doesnt have the side effects of the first, of diarrhea in a disease that is so physically debilitating, is.
By my count, this happened about 100 years (+/-) too late to save whatever is left of the FDA.
@adamfeuerstein
·
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EXCLUSIVE --> Biogen’s $BIIB Samantha Budd Haeberlein, an architect of Aduhelm, leaves company https://statnews.com/2023/03/12/biogen-samantha-budd-haeberlein-leaves-company-aduhelm/
Her departure comes two weeks after Billy Dunn left the FDA.
statnews.com
Biogen's Samantha Budd Haeberlein, an architect of Aduhelm, leaves company
Samantha Budd Haeberlein, the Biogen senior executive who supervised the development and controversial approval of the Alzheimer’s treatment Aduhelm, has left the company, STAT has learned.
12:01 PM · Mar 12, 2023
Joseph K
Multiple vouchers for same rare pediatric disease. On this list, numbers 7, 9, 21, 24, and 29 are all priority review vouchers for drugs treating Duchenne muscular dystrophy; and 18 and 20 are both for Cystic fibrosis.
"Priority Review Vouchers for rare pediatric diseases, issued and sold 2012-present"
https://www.kidsvcancer.org/priority-review-vouchers/
Two questions seem relevant to some extent..
- may a rare pediatric disease voucher be issued for a disease that already has an approved treatment?
- has the same disease ever received
two pediatric rare disease vouchers?
Hoskuld
Some are diagnostic companies, some sell services or precursor products. There are not 6,653 biotech companies seeking approval for one or more drugs.
attathehunt
"Pretend that Pfizer or Merck or Roche executives were in boardroom talking about Anavex's hiring of a competent biostatistician who knows exactly what the FDA needs to see, What do you think they are saying about it? "
Excellent work SOKOL
chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://79bcf7a1-8b8e-483b-b7cf-f5c5192a6d63.usrfiles.com/ugd/79bcf7_c5813c517d9f4ca5aacbeb719508827a.pdf
In other words, Blarcamesine restored dysregulated genes associated with Alzheimer's and Parkinson's. If so, was that restoration evident in all patients treated with Blarcamesine versus no restoration in the placebo patients? More importantly, did all treated patients show some degree of improvement or decline in the progression of the diseases? Or was it that the restoration occurred only in those patients treated with the Blarcamesine high dose?
It's all about connecting the right DOTS.
Agree w jonJ...a clear message of AVXL leadership which would not(could not) be sent w/o strong-credible science and clinical evidence support.
Hey, WHAT COLOR IS THIS RED PIECE OF PAPER????[b[/color]
NEW YORK, March 09, 2023 (GLOBE NEWSWIRE) -- Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, today announced the appointment of Kun Jin, Ph.D., as Vice President, Head of Biostatistics.
"Dr. Jin will draw on his extensive experience, including recently as the Statistical Team Leader at the U.S. Food and Drug Administration (FDA). Dr. Jin provided statistical review coverage and expertise for neurological drug products for the Center for Drug Evaluation and Research (CDER), and performed timely and quality reviews of marketing applications, including New Drug Applications (NDA), Biologic License Applications (BLA), and Investigational New Drug (IND) applications. Under the leadership of Dr. Jin, the neuropharmacological statistical team has completed several hundred statistical reviews of NDAs, BLAs, and efficacy supplements[color=red][/color].
"March 9, 2023 07:18 AM EST R&DPharma
Ten years later, Lilly's long-term Alzheimer's trial of solanezumab has definitively failed
Drew Armstrong
Executive Editor
A trial of Eli Lilly’s Alzheimer’s drug solanezumab that began in 2013 didn’t show any benefit in patients, who were followed for a decade to try and answer whether the amyloid-targeting drug might slow the disease.
GREAT NEWS TODAY!!!...georgejji
https://www.anavex.com/post/anavex-life-sciences-appoints-former-fda-lead-neurology-statistician-as-vp-head-of-biostatistics...
Agree, this should be seen as good news. Any thoughts on why (someone-Mr. Market) has not shown a positive or at least not (sp) negative reaction?
attilathehunt SeeEE??? You were right...
Number 70 also relates to abundance and money. This can manifest itself in a variety of ways including the perfect job, lottery winnings, and other unexpected gains. This can also make life easier for you and your family as well.
attlathehunt
Like I said....Watch those options!
Everyday the call options volume inches up...Someone is accumulating and they know they have a little time...I suspect next week they won't hold back.
Sigma receptors are also involved in the complex processes of cholesterol homeostasis and protein folding. While previous work on this topic has been limited, research has been conducted in multiple disease states, such as addiction, aging. Alzheimer’s disease, cancer, psychiatric disorders, pain and neuropathic pain, Parkinson's disease, and others. There is currently increasing interest in sigma-1 and sigma-2 receptors as they provide potential therapeutic targets for many disease indications.
abew4me
AVXL is the only stock in my portfolio that is green today...and it's the largest investment too!
10.00+0.07 (+0.70%)
As of 11:50AM EST. Market open.
Any idea what this is worth? Supporting WW info?
Well Done:
"Our proprietary SIGMACEPTOR™ discovery platform produces therapeutic candidates that lead to the modulation of SIGMAR1. Data suggests that activation of SIGMAR1 results in the restoration of complete housekeeping function within the body and is pivotal to neural cell homeostasis and neuroplastici["/b]
Some day soon we will get notified to man our battle stations. Be ready, there will be no warning. It is an experience you will never forget.
georgejji
Expect 76 or more super responder from the Anavex Phase 2b/3 early Alzheimer’s trial. Remember a super responder actually improves over time better than when they started taking Blarcamesine. For super responders blarcamesine doesn’t just slow the progression of Alzheimer’s disease it actually reverses the disease.
For the OLE extension expect 230 or more super responders.