7 ms·
Alzheimer’s disease can be reversed in animal models? Study
- 7thpower 11mo agoThis is great news for mice who have something vaguely similar to Alzheimer’s.
- A_D_E_P_T 11mo agoThe authors report that restoring NAD+ balance in the brain -- using a compound called P7C3-A20 -- completely reversed Alzheimer's pathology and recovered cognitive function in two different transgenic mouse models (one amyloid-based, one tau-based). The mice had advanced disease before treatment began. Three comments: - You can actually buy the drug here: https://focusbiomolecules.com/p7c3-a20-nampt-activator-proneurogenic-agent/ https://focusbiomolecules.com/p7c3-a20-nampt-activator-prone... It's a simple small molecule. If this stuff works, expect it to be everywhere within just a couple of years. - There's room for skepticism. As Derek Lowe once wrote: "Alzheimer's therapies have, for the most part, been a cliff over which people push bales of money. There are plenty of good reasons for this: we don't really know what the cause of Alzheimer's is, when you get down to it, and we're the only animal that we know of that gets it. Mouse models of the disease would be extremely useful – you wouldn't even have to know what the problem was to do some sort of phenotypic screen – but the transgenic mice used for these experiments clearly don't recapitulate the human disease. The hope for the last 25 years or so has been that they'd be close enough to get somewhere, but look where we are." > https://www.science.org/content/blog-post/just-how-worthless-are-standard-alzheimer-s-models https://www.science.org/content/blog-post/just-how-worthless... - If the drug's mechanism of action has been correctly assigned, it's very plausible that simply supplementing with NMN, NR, or NADH would work equally well. The authors caution against this on, IMO, extremely shaky and unjustified grounds. "Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer."
- bossyTeacher 11mo ago> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. Does this mean that people are having to trade Alzheimer in exchange for high risk of cancer? Or does this mean that we need better precursors that don't require that trade off?
- juujian 11mo agoIt's a quality of life vs years left calculation you have to make on a case by case basis.
- mmooss 11mo agoYou can't make calculations without data, and in this case you have none: we have no idea of the effects on humans.
- shawnz 11mo agoKeep reading: > Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels.
- luma 11mo agoI think it means one should read the very next sentence: > Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels.
- A_D_E_P_T 11mo ago
- ltbarcly3 11mo agoThey mean the fake Alzheimer's they induce by injecting poison into 3 month old animals or which develops in mice genetically engineered to have diseases that aren't Alzheimer's but are somewhat similar to Alzheimer's in some ways, not the kind where you wait 70 years for a human to develop which they don't even really understand what causes it.
- gus_massa 11mo agoAgree. As far as I remember, mice don't get real Alzheimer, so they only have a model that is somewhat similar. Let's hope the cure can be transfered to humans, but I think the chances are extremly low.
- timcobb 11mo agoYeah, we got it!
- busyant 11mo ago> the fake Alzheimer's they induce .... I used to work with a guy who had been a scientist at a large pharma company (we were both working at a small biotech start-up at the time). He told me an interesting story... basically, scientists at his company would get an extra year-end bonus if they had worked on a drug candidate that made it past animal studies and into human (clinical) trials. He told me that one way to 'consistently' get the extra bonus was to work on candidate drugs for neurological diseases (e.g., Alzheimer's, etc.) because ... the animal models for those diseases were (generally) dog shit, so it was easy to find a drug that 'cured' whatever happened to be your neurological disease of interest in mice/rats/etc. Then you get your bonus and the drug fails in humans. Lather, rinse, repeat.
- jtrn 11mo agoThis is totally improper reporting of the study. When enough words, framing, and unstated important premises are omitted, it crosses over from the realm of incomplete or misleading into plain outright lying in my worldview. They claim "Reverses advanced AD in mice." What they did is reverse symptoms in genetic models. They claim to "Restore NAD+ homeostasis," ignoring that NAD might not even be causally related to Alzheimer’s, just a side effect. It’s like saying we cured a house fire because we efficiently removed the ashes after the fire. It’s the Tau thing all over again. The claim: "Conservative molecular signatures" when in reality, 5xFAD mice are poor predictors of human clinical success to such a degree that it’s statistically more common for mice studies to NOT transfer to human biology than to do so. They also make unsupported claims like "Safer than NAD+ precursors (supplements)," when this is a pre-clinical assumption. No human toxicity trials are mentioned in this context, and there are always MASSIVE differences when switching to real human studies. It might be correct, but there’s no basis to say that based on this study. Also, the senior author owns the company. The paper has the hallmarks of a "pitch deck" for the drug. In short, it seems to me that the claim of "Full Neurological Recovery" is misleading to patients. It fails to prove that fixing NAD+ in humans will stop the disease, only that it works in mice engineered to have the disease, and only by assuming that their specific measure is a 1-to-1 with the clinical presentation of the disease. The results are likely the "best case scenario" presented to support the commercialization of P7C3-A20. Here is the COMMON SENSE question peer-reviews should have asked. Is low NAD+ the fire, or just the ashes? Why should we believe this works in humans when the last 500 'cures' in 5xFAD mice failed? Are you regrowing a brain, or just cleaning up a dirty one? How does one molecule fix five unconnected problems simultaneously? The Context: The drug fixed inflammation, blood-brain barrier, amyloid/tau (protein folding), and memory (neuronal signaling). Drugs rarely hit four distinct biological systems with 100% success.... Where is the toxicology report that proves 'safer than supplements'?
- exmadscientist 11mo agoI can't upvote your comment enough. Please... people, do not get your hopes up over this one PR pump piece released on Christmas Day. This is not a legit study. (It might, perhaps, somehow, still be correct, perhaps... even broken clocks are right twice a day... but it's still not a legit study.)
- briandw 11mo agoBoosting NAD has a been the focus of taking NMN supplements. Seems like NMN is a dud for boosting NAD. I wonder if P7C3-A20 can be used instead?
- ganesh7 11mo agoThis is eyewatering. My father and grandfather died early due to this condition. Hope for many.
- beckerdo 11mo agoIt's a useful discovery. The real proof and utility is if what they learned from "mouse-heimer's" can be applied to human Alzheimer's.
- nandomrumber 11mo agoThat’s so obvious I can’t believe I didn’t think of it, and / or that I haven’t seen it before. Mouse-heifer’s! <knee slap>
- looneysquash 11mo ago"Animals" suggests more than one kind of animal. Which animals besides mice does this cause a full neurological recovery in?
- cubefox 11mo agoRelated: Recently another study on a mouse model had similar effects when using lithium orotate: https://www.science.org/content/blog-post/lithium-deficiency-and-alzheimer-s-disease https://www.science.org/content/blog-post/lithium-deficiency...
- jrpt 11mo agoThere’s a lot of umbrella diagnoses that would benefit from more specific diagnostics first. What we call Alzheimer’s is probably actually caused by number of different causes depending on the person. This is true of a lot of things in medicine that get grouped together. That’s why testing a drug in mouse models with all the same characteristics sometimes works but fails to translate into humans who have more variety amongst each other. The same is true of many diagnoses like pneumonia, cancer, alopecia, essential tremor: there’s multiple different groups that would benefit from different things, and if we had better ways to identify the groups, we’d give them what works for them instead of wasting their time with the wrong treatment. As an example, antibiotics won’t work for viral pneumonia and in addition to wasting the patient’s time, actually harm your microbiome. If you had a perfect way to know which is which, you’d always get the right treatment. Precision medicine takes this even further.
- djmips 11mo agoAlways profile before you optimize.
- JumpCrisscross 11mo ago> Always profile before you optimize Not necessarily. Often, treatment and testing can be done in parallel. In many cases, the treatment is also a test. Every time you apply topical antibiotics to a cut, you’re testing for antibiotic resistance.
- awesome_dude 11mo agoI had read their comment as "accurately diagnose before treating" It's not "House" where you guess something, provide a treatment, watch as things get worse, then change diagnosis in the real world is it?
- JumpCrisscross 11mo ago> read their comment as "accurately diagnose before treating" Right. And I’m arguing that’s more of a fiction than House. In most cases, waiting for a definitive test can be more harmful than treating when the preponderance of evidence points one way. (In some cases, the test is riskier than the treatment.) Broadening out of medicine, it’s absolutely okay in many circumstances to try a fix before you’re sure you know what the problem is.
- xvxvx 11mo ago[flagged]
- kingofmen 11mo agoDo you eat meat?
- ssstt 11mo agoIf you don’t want to be complicit you can always stop taking any drug
- deleted 11mo ago[deleted]
- fredoliveira 11mo ago
- bilsbie 11mo agoGOOD point by my wife, how does this affect those with apoe4 status. And also is there any connection with the recent lithium findings.
- 1970-01-01 11mo agoYet another "in mice" breakthrough. The cerebral cortex of a mouse has around 8–14 million neurons while in those humans there are more than 10–15 billion. So scale this outcome by literally 1000x more neurons and wake me when the chimps are remembering how to hold a long conversation.
- JumpCrisscross 11mo ago> Yet another "in mice" breakthrough I don’t get this take. Like yes, we aren’t mice, and everything that works in mice won’t work in humans. But loads of things that worked in mice did wind up working in humans, which is why most groundbreaking drugs over the past decades were first explored in mice, which is why we continue to use mouse models.
- jmward01 11mo agoNot my field, but I think a big point here is this isn't purely researching into Amyloid plaques. It is way past time to explore many other possibilities and it is promising to see research in a different direction. This isn't to say Amyloid plaques aren't worthy of research, but when you slam into a wall for a few decades then maybe you should look in different directions now and again.
- tbenst 11mo agoA key challenge with Alzheimer’s is there is no good mouse model for the disease. While some approximate the phenotype, it’s not clear that the disease model as commonly studied in mice matches well with mechanisms of the human disease. There’s some thinking in the field that this could be a key reason why so many treatments have appeared very promising in mice and haven’t panned out in humans.
- londons_explore 11mo agoI really don't see how you can make an animal model of something you don't fully understand in humans. Just because you made an animal have similar symptoms doesn't mean the animal has Alzheimer's! I suspect that animal models hinder rather than help science progress because most of the animals models will turn out to be entirely wrong.
- kinj28 11mo agoMy cofounders mom had got Alzheimer’s at rather younger age of 60 something. It grew extremely rapid and within 2 years she grew into a vegetative state. Given how I have seen different patients and varying pace of dementia growth - I somehow think Alzheimer’s must have multiple sub families & may appear same but must be behaving differently from their onset.
- mbrochh 11mo agoUsual PSA: Don't wait for a cure for Alzheimers. Work towards not getting it in the first place. Alzheimers is "brain diabetes". You get it from consuming sugars and carbs. It can be easily avoided.
- hnarn 11mo agoWhat a ridiculous statement. By your logic, anyone with alzheimer’s got it from eating sugars and carbs and simply didn’t choose to avoid it. Sugars and carbs also keep you alive. Please keep your mortality neurosis to yourself.
- Adrian_Vanessa 10mo ago[dead]