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Thanks for this. It's a very well thought out theory based on a large number of patients in studies. I think it could play a role in the success or failure of Sava's drug later this year. Hoping for a positive outcome
A study shows that rising levels of brain protein Aß42, not the reduction of amyloid plaques, better explains the cognitive benefits of new Alzheimer’s drugs. This finding challenges the traditional focus on plaques in Alzheimer’s treatment.
A new study reveals that the rise in protein levels due to new Alzheimer’s drugs may explain the slowing of cognitive decline just as effectively as the reduction of amyloid plaques.
In a study that questions the effectiveness of newly approved monoclonal antibodies in reducing cognitive decline in Alzheimer’s patients by clearing amyloid, researchers from the University of Cincinnati discovered that an unintended rise in a critical brain protein’s levels correlates just as strongly with cognitive benefits.
Led by UC’s Alberto Espay, MD, the research was published in the journal Brain.
Study background
For decades, the prevailing theory in the field has stated that a protein made up of 42 amino acids called amyloid-beta 42 (Aß42) hardens into clumps called amyloid plaques, and those plaques damage the brain, causing Alzheimer’s disease.
Espay and team have hypothesized that normal, soluble Aß42 in the brain is crucial for neuron health and that the loss of Aß42, rather than the buildup of plaques, drives Alzheimer’s. This includes published research that suggests dementia occurs not when plaque levels are high but when Aß42 levels drop very low.
According to Espay’s research, the transformation of Aß42 into plaques appears to be the brain’s normal response to biological, metabolic, or infectious stress.
Alberto Espay
Alberto Espay, MD, MSc, professor of neurology at the UC College of Medicine and Director and Endowed Chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders. Credit: Colleen Kelley/UC Brand + Creative
“Most of us will accrue amyloid plaques in our brains as we age, and yet very few of us with plaques go on to develop dementia,” said Espay, professor of neurology in the UC College of Medicine and director and endowed chair of the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders at the UC Gardner Neuroscience Institute. “Yet the plaques remain the center of our attention in biomarker development and therapeutic strategies.”
Study details
Recently, several new monoclonal antibody medications designed to remove amyloid from the brain were approved after showing they lessened cognitive decline in clinical trials.
Espay and his colleagues noticed that these drugs unintentionally increased levels of Aß42.
“Amyloid plaques don’t cause Alzheimer’s, but if the brain makes too much of it while defending against infections, toxins, or biological changes, it can’t produce enough Aß42, causing its levels to drop below a critical threshold,” Espay explained. “That’s when dementia symptoms emerge.”
The team analyzed data from nearly 26,000 patients enrolled in 24 randomized clinical trials of these new antibody treatments, assessing cognitive impairment and differences in levels of Aß42 before and after treatment. They found that higher levels of Aß42 after treatment were independently associated with slower cognitive impairment and clinical decline.
“All stories have two sides — even the one we have told ourselves about how anti-amyloid treatments work: by lowering amyloid,” Espay said. “In fact, they also raise the levels of Aß42. Even if this is unintended, it is why there may be a benefit. Our study shows that we can predict changes in cognitive outcomes in anti-amyloid trials at least as well by the increases in Aß42 as by the decreases in amyloid.”
Espay said these findings fit well into his larger hypothesis about the root cause of Alzheimer’s, as increasing levels of Aß42 appear to improve cognition.
“If the problem with Alzheimer’s is the loss of the normal protein, then increasing it should be beneficial, and this study showed that it is,” he said. “The story makes sense: Increasing Aß42 levels to within the normal range is desirable.”
However, Espay believes these results also present a conundrum for clinicians because removing amyloid from the brain is toxic and may cause the brain to shrink faster after antibody treatment.
“Do we give patients an anti-protein treatment to increase their protein levels? I think the end, increasing Aß42, doesn’t justify the means, decreasing amyloid,” Espay said. Therapies that directly increase Aß42 levels without targeting amyloid are a focus of research for Espay and his group
Per 10q company finally gained synthetic bioequivalence. Of course only matters if they start additional trials
Thanks Doc. Yes more of an interest in the science at this point and sounds like even that's a long way off.
Here's a link to the trial on clinicaltrials.gov
https://clinicaltrials.gov/study/NCT06190912#participation-criteria
From inclusion criteria, it looks like this phase 1 will have a broad range of patients from no disability (EDSS 0) to using a walker (EDSS 7.0) and can have any form of MS (RRMS, SPMS, PPMS). This is open label with everyone receiving 14 doses over 26 weeks (similar dose as in the AD trials) and patients will continue on their existing MS medication. They can be on a stable dose of any MS med except teriflunomide (likely due to concerns of additive liver toxicity)
Cleveland clinic is one of the largest MS centers in the country and has access to a 7T research MRI, though all the MRI measures mentioned in the outcomes would be possible on a commercially available 3T (though not on 1.5T). However, Diffusion MRI and myelin water fraction will be more informative on a 7T. Though not on the list, I would expect them to also analyze paramagnetic rim lesions and grey matter lesion if the 7T is chosen.
If it is ever shown to have a benefit in MS, I suspect that bryostatin, based on MOA, would have more value in progressive MS than in earlier inflammatory/relapsing MS. With patients already on another DMT and with full range of disabilities in a small population for only 40 weeks, proving any clinical benefit will be very difficult in this study. Rather, I believe they are trying to prove a biologic effect and then will need to raise many millions to run a P2 for 2 years. From a science perspective this is very interesting but with a company having limited funds, the financial risk of investment is extremely high. A successful P1 trial still leads to a drug requiring many years of testing in a difficult indication
Wow SAVA getting killed today
Is this dog pile the next SAVA? Fingers crossed for the snake oil pumpers..
I do like the advanced MRI imaging for biomarkers. Could help in future AD studies hopefully. More science and less guess work.
A couple more months of conversion to dirt cheap shares theft and then the price should escalate up to something closer to reasonable market value.
For some context, the press release mentions $26.3 million in cash with a low burn rate and indications that are alive (MS in particular) while the current market cap is just over $5 million... These assholes have no shame with their blatant theft in the "regulated" public capital market...
It's good news. A bit delayed. Cleveland Clinic will run the trial and it will take a couple years. Doc would be a good one to comment as I believe this is his area of expertise. I would love to see an IND for FragileX but not sure of it's status if any. Seemingly telling that company hasn't mentioned AD in a long time.
Runn...your thoughts on today's news pls?
NEW YORK , June 26, 2024 /PRNewswire/ -- Synaptogenix, Inc. (Nasdaq: SNPX) (" Synaptogenix " or the "Company"), an emerging biopharmaceutical company developing therapeutics for neurodegenerative disorders, today announced that the Food & Drug Administration (FDA) has authorized an Investigational New Drug (IND) application for Bryostatin-1 as a potential treatment for multiple sclerosis (MS).
NEW YORK , June 26, 2024 /PRNewswire/ -- Synaptogenix, Inc. (Nasdaq: SNPX) ("Synaptogenix" or the "Company"), an emerging biopharmaceutical company developing therapeutics for neurodegenerative disorders, today announced that the Food & Drug Administration (FDA) has authorized an Investigational New Drug (IND) application for Bryostatin-1 as a potential treatment for multiple sclerosis (MS).
Perpetual snake oil trash. Company will never amount to anything but robbing hopium holders.
I don't think they are going to PR anything that would help the stock price. There is still several months of low priced stealing to occur...
Yeah I like COYA as well. NRSN put out additional results this morning showing a positive trend that hopefully allows a successful P3 trial in ALS as well.
The papers emphasize a common theme: Inflammation.
Another interesting theme is drug delivery using targeted Exosome carriers (T-Helpers).
$COYA is another biotech following a similar path but focusing on ALS.
Yeah there are several. Most of the work has been done by Johns Hopkins. Long ways off.
https://www.pnas.org/doi/full/10.1073/pnas.1719902115
https://pubs.rsc.org/en/content/articlelanding/2022/bm/d1bm01142a
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00625/full
https://www.sciencedirect.com/science/article/pii/S2451945620305249
Surprising.
Any more research papers backing this P1 trial?
According to the FDA clinical trials website the MS trial is now recruiting. It's a couple months later than the last site update but status went from "not recruiting" to "recruiting the last couple days. No idea if the company ever PRs this as the Cleveland Clinic is running the show. Maybe the upcoming quarterly (next week or two) will mention it. Long road until trial completes. We're talking 2026 most likely.
Not any time soon there isn't
Monster potential here ... SNPX
Doc, just wondering if you are continuing to follow Tiziana and if you had any thoughts regarding their progress. Best wishes.
https://www.globenewswire.com/news-release/2024/04/18/2865243/0/en/Tiziana-Life-Sciences-Announces-New-Quantitative-PET-Imaging-Data-on-Foralumab-at-the-Annual-Meeting-of-the-American-Academy-of-Neurology.html
Just like all the alternative AD drugs that have failed in AD unfortunately.
This shell was a trading vehicle, bryostatin failed multiple times. Insiders knew this. It's all linked in my sticky.
Synaptogenix Increases Stake in Innovative Psilocybin Drug Discovery Company through its Partnership with Cannasoul Analytics
https://ir.synaptogen.com/news-releases/?qmodStoryID=7600649204374859
Totally understand. Hoping for the best!
I had kept few for ol' times sakes(that now got slashed by 1/25- post RS), so have only a piddly few left. If something good comes of this, will celebrate not in terms of $$ but for the dreaded disease.As long as Dr.Alkon is alive here I will hold, but like you no big hopes for me either. Good luck on everything runn
If I owned it, I would be looking for a possible MS trial or something similar to create a nice bump on this low float. There will be no trial readouts in 2024 or 2025 that I can see. I hope for the best with this drug, but it hasn't been investable since the trial failed well over a year ago. Jmho
Not been around for a bit, seeing that our SNPX has had an RS recently.Nice action since, maybe we dare to get our hopes up again runn,lol?
Dog pile heading to the bargain bin in short order. Book it. The masters of charletry.
Low floater now. Haven't owned in awhile. Could have a move if they ever announce the MS trial I suppose
SNPX...FREASH OFF THE SPLIT...
I noticed the SAVA results today. It’s a small play for me.
I’m still invested in some AD plays including Synaptogenix.
Some reasonably good results on Sava today so at least a few alternative plays still out there. Hoping bryostatin gets another shot on moderate AD as it seems to be the only one with a shot at halting the disease. Looks like the MS trial kicks off this month. I'm not in any of the AD plays at the moment in full disclosure.
https://www.clinicalleader.com/doc/was-fda-wrong-annovis-bio-shows-strong-data-and-no-side-effects-0001
Article regarding Annovis is from 2021. It mentions Tau- they have a Parkinson’s read out coming in next 7 weeks and AD second quarter. PD is looking interesting.
Tell it to the Cleveland Clinic. They are running the trial.
The replied to post contains my old sticky on this scam...
The racket is still the same...
Bryostatin trial finally gets registered with details. Starts this month. 20 patients. Essentially same dosing as previous AD trial with 2 cycles and a follow up 12 weeks after final dose fyi.
https://classic.clinicaltrials.gov/ct2/show/NCT06190912?term=bryostatin&draw=2&rank=1
read a lot of reviews on Cortexi: forget about it.
Anybody look at the Cortexi video? Claims to eliminate tennitus in six weeks and hint at helping als,hearing, and dementia also. Combination of Asian herbs. Regrows support cells at cochlear cells. (sp?)
This research method is known as "Barking up the wrong tree"....
Thank you. Yeah. They mentioned "Rockefeller" in W. Va multiple times.
I didn't see it but have read in the last week or so about the ultrasound waves aiding in plaque/tau reduction. What I had read had come out of West Virginia University where Bryostatin and Alkon had done much of their research so it could be a promising avenue. All that is dependent on how big of a problem plaque really is, which of course it up for debate. It's certainly interesting to follow and hopefully makes the anti-plaque drugs more effective with less side effect.
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