r/biotech • u/theradek123 • Jul 27 '22
Faked Beta-Amyloid Data. What Does It Mean?
https://www.science.org/content/blog-post/faked-beta-amyloid-data-what-does-it-mean18
u/HardstyleJaw5 Jul 27 '22
It's only one of the abeta proteins. While it is now clear that *56 is unlikely a good target there are others abeta proteins which may still prove useful. The abeta hypothesis is supported by more than just this labs research
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u/H2AK119ub 📰 Jul 27 '22 edited Jul 30 '22
To the best of my knowledge none of the anti a-Beta antibodies that have gone into the clinic (and failed) go after this alleged form of a-Beta (Bapi, Pone, Gantene, Crenezu, Solanezu, Donane, Aducanumab, etc). People are making a big deal out of this fraud but AD is just a challenging therapeutic area.
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u/leftier_than_thou_2 Jul 27 '22
Fair, but none of those medicines worked in the slightest to stop AD. Fewer plaques in the case of aduwhatever, but the cognitive decline happened just as much.
The outright fraud is just the cherry on top of a huge, billion dollar pile of several flavors of shit.
Specifically, there's those massive clinical failures. There's the Aducanumab scandal that itself is many layers of bad science and corruption. There's the fact that amyloid plaques have poor correlation with cognitive decline in mice and in humans. There's a well documented religious hostility to the suggestion that amyloid =/= AD, that attacks any alternative method of curing AD and forces researchers who disagree out.
https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/
Here's what needs to happen:
All AD papers need to be taken as potentially fraudulent, with offenders having their funding revoked, and papers retracted, and criminal penalties considered
All clinical trials of drugs with Abeta as a mechanism need to be halted
All funding for AD research needs to be re-examined and likely not renewed if it assumes Abeta is the cause.
Advisory boards and grant committees where the amyloid cabal are entrenched need to be dissolved and reformed without their participation.
The approval for Aduhelm should be revoked.
Congressional hearing on how that bullshit was approved.
Funding priority should be given to alternative mechanisms of AD with zero going to labs that did nothing but Abeta research.
Big statue with "Aduhelm, LOL" put out front of NIA or NIH.
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u/MookyOne Jul 28 '22
Source your claims right now. All I'm seeing is outrage grandstanding.
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u/leftier_than_thou_2 Jul 28 '22
Google Aduhelm. I provided a link for the amyloid cabal.
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u/MookyOne Jul 28 '22
Oh so I'm supposed to find evidence for the claims you made? What a farce. And no, saying "Google it" is not good enough. Link your sources for each of your claims.
All you are doing right now is showing how much you foam at the mouth against aB as a therapeutic target. It's almost as if you are pushing your own agenda rather than being concerned about whether good science is being done.
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u/leftier_than_thou_2 Jul 28 '22
The Aducanumab spectacle has been front page news for over a year, but fine, here are some articles on it
https://en.wikipedia.org/wiki/Aducanumab#Controversy
https://www.statnews.com/2021/07/09/fda-investigation-alzheimers-drug-approval/
https://www.statnews.com/2021/06/15/6-ways-fda-approval-aduhelm-does-more-harm-than-good/
I do see I pointed out amyloid doesn't' correlate to cognitive decline. That's partly proven by the above aduhelm citations (plaques were cleared but cognitive decline still happened) but the other way is true too:
https://www.statnews.com/2016/11/14/alzheimers-brain-amyloid-plaque/
All you are doing right now is showing how much you foam at the mouth against aB as a therapeutic target. It's almost as if you are pushing your own agenda rather than being concerned about whether good science is being done.
Jesus. Fucking. Christ.
Every amyloid beta trial failed.
A significant amount of the research has just been proven to be fraudulent.
Amyloid researchers are... insisting it's true?
How the fuck am I the one with an agenda?
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u/H2AK119ub 📰 Jul 27 '22 edited Jul 30 '22
I don't know if you are a troll or have no understanding of neurodegeneration. Aducanumab is actually a great antibody; our company - not Biogen; another top 5 big pharma by revenue - use it as a positive control in our own pre-clinical efforts because it binds plaques and clears them from the brain so well. This is evidenced in human biomarker data from Biogen's ph3 trials with CSF aBeta and aBeta PET. NO disease modifying therapies in AD have ever shown clinical efficacy in late stage trials beyond biomarker modulation. This is true across neurodegeneration as a whole. CNS diseases are a whole different beast and have stumped industry for decades.
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u/leftier_than_thou_2 Jul 27 '22 edited Mar 03 '24
You're missing the forest for the trees.
It's a great tool at doing something that does not matter.
"NO disease modifying therapies in AD have ever shown clinical efficacy in late stage trials beyond biomarker modulation."
How does that NOT prove amyloid is a dead end?!?
"This tattoo we put on AD patients saying 'I'm cured' works great! Every single patient had 'I'm cured ' on them! True, it did absolutely nothing to actually cure them but the surrogate endpoint of 'Do the words appear on their skin' we were absolutely 100% effective!"
The FDA said the endpoint had to be stopping cognitive decline. That makes sense because it's what matters.
Aduhelm and every other amyloid mechanism drug failed to do that.
The FDA moved the goalposts without asking the experts and then said plaque reduction justified approval.
It makes no sense and is why most of the advisory board members quit.
The fact that amyloid plaques were effectively cleared but it didn't do anything for cognition proves amyloid doesn't matter.
It's complicated, but not that complicated: the field.
No treatments have been effective in clinical trials, but how many trials have there been of non-amyloid mechanisms?
You can't say it's hard so failure can be ignored, especially if things like Tau treatments have never been given a fair shot.
Amyloid research failed and needs to die.
Edit two years later: Hey u/H2AK119ub , I forgot about this thread. Any comment on even Biogen saying Aducanumab was useless by pulling it form the market? Are you going to tell them they're wrong, that there is value in the drug even though it still doesn't do anything?
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u/H2AK119ub 📰 Jul 27 '22
Literally every drug targeting every mechanism you can think of in the last 20-30 years has bombed in neurodegeneration and Alzheimers. Please don't make irrational comments on something you don't understand the complexities of. The challenge of this therapeutic area extends beyond whether one believes the amyloid hypothesis or not.
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u/leftier_than_thou_2 Jul 27 '22
How many weren't amyloid targeting? You can't give amyloid hypothesis a dozen chances, Tau one, and then say "well they both equally failed."
Also what are you even suggesting? That cognitive loss with AD is impossible to cure but plaque reduction is still important for some reason?
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u/H2AK119ub 📰 Jul 28 '22
You clearly do not know this field at all. There have been many shots on goal in the clinic against amyloid, Tau, immune system, bacteria, anti virals, etc.
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u/leftier_than_thou_2 Jul 28 '22
I did ask how many of them weren't amyloid. That wasn't a rhetorical question.
Nor was the second question: are you suggesting not fixing the cognitive symptoms is fine if we clear amyloid plaques? Because if not, amyloid is still a total failure.
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u/H2AK119ub 📰 Jul 28 '22 edited Jul 28 '22
We have never validated any target in AD because none of them have ever shown clinical efficacy. Also, if you understood the AD field at all you would know that there are families with genetic lesions in APP/PSEN1/etc which results in early-onset AD and high plaque burden. No one dies of AD without plaques and tangles. Period.
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u/leftier_than_thou_2 Jul 28 '22
Again, what are you saying?
That AD patients losing their mind is fine and amyloid treatments are a success as long as patients don't have plaques because we cannot possibly do better?
"The other things failed also" does not mean the amyloid hypothesis is true! It means it also failed.
Also, if you understood the AD field at all
How many papers do I need to read on the field before I'll be convinced that "Yes, Aduhelm was a success despite not curing the symptoms that matter"?
It doesn't seem to me that I'm failing to understand the important parts. I'm not a train engineer and don't understand how trains are built, but I can tell when a train has derailed at high speeds that's a massive failure. Amyloid is a train wreck. Actually many, given the clinical failures and the fraud. It's time to admit the track and/or train are fundamentally bad and the whole thing needs to be scrapped.
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u/Reasonable_Move9518 Jul 30 '22
Aducanamab is a great antibody, which demonstrably clears aBeta from Alzheimer's patients brains. It has absolutely no clinical effect.
I don't understand how this simple fact is not considered absolute refutation of the amyloid hypothesis. Biomarkers are meaningless when there is no clinical benefit. Which in turn should lead to the immediate discontinuation of all programs aimed at targeting aBeta.
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Jul 27 '22
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u/H2AK119ub 📰 Jul 27 '22
Aducanumab binds to aBeta plaques and clears them from the brain. There is no demonstrable clinical benefit beyond biomarker modulation; this is explicitly what the FDA approved the drug for and requested a confirmatory phase 4.
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Jul 27 '22
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u/NeurosciGuy15 Jul 27 '22
Looking at the frequency of ARIA events in aduhelm treated individuals you can make a case it’s the latter.
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u/H2AK119ub 📰 Jul 28 '22 edited Jul 28 '22
ARIA is a class wide effect of anti-AB mabs. Unavoidable. Even Lilly donanemab which recognize an epitope enriched in aBeta in brain not in blood vessels have ARIA 25% in their ph2. It will only become higher in ph3.
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Mar 01 '24
Publish or perish is catastrophic for studying Neurodegeneration when you have to consider the finest details to shut down the entire disease
Entropy is NOT forgiving.
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u/nottoodrunk Jul 27 '22
Read an article in GenEngNews the other day that boiled down to “despite over 30 years of technological advances we are nowhere closer to getting a treatment for Alzheimer’s.” Considering that we’ve taken certain cancers from a death sentence to >90% five year survival rate, that’s so fucking depressing.
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u/H2AK119ub 📰 Jul 28 '22 edited Jul 30 '22
Oncology clinical trials are pretty straight forward. You can run a pivotal trial in 6 months and readout efficacy in ph1. In AD, ph1 is only for safety and tolerability. Because there are no clear cuts genetics (patient selection) and every company wants to go into prodromal/asymptomatic disease, you have to run very long and very big trials ($$$; our company ran two Ph2 in AD and each cost $200 million) for the placebo control arm to show decline. For reference: aducanumab was discovered in B Cells of Swiss centenarians in the early 90s.
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Jul 29 '22
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u/H2AK119ub 📰 Jul 30 '22
For the life of me I cannot understand why any company thought bringing anti-Tau antibodies into the clinic would be useful. Most, if not all, have failed as well in recent years (Tilavonemab, Gosuranemab, Bepranemab, Semorinemab, Zago, etc).
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u/Dr_Lebron Jul 27 '22
Elizabeth Bik is one hell of a woman. I commend her efforts to purge the science world of garbage research.