7 ms·
New nanotherapy clears amyloid-β, reversing symptoms of Alzheimer's in mice
- 317070 1y agoThe paper: `Rapid amyloid-β clearance and cognitive recovery through multivalent modulation of blood–brain barrier transport` https://www.nature.com/articles/s41392-025-02426-1 https://www.nature.com/articles/s41392-025-02426-1 "Cognitive assessments revealed that treated AD mice exhibited significant improvements in spatial learning and memory, with performance levels comparable to those of wild-type mice. These cognitive benefits persisted for up to 6 months post-treatment." I'm curious if Derek Lowe will comment on this on his blog. I'll await his opinion on how much we ought to celebrate here. He's not a big fan of the amyloid hypothesis and has worked many years in this exact field, so I reckon he will point out why skepsis is warranted.
- underdeserver 1y agoYup. I hope he says something about what "nanotherapy" means.
- anon84873628 1y agoMy biggest criticism of the article is emphasizing "nanotechnology" when it is really just an extra large synthetic molecule. I mean, it is nanotech! But just not the type most readers would imagine. They could have elaborated on an justified this better by explaining novel synthesis method or something.
- mattkrause 1y ago(N+1)th time's the charm! I do sincerely hope that we find something for Azheimer's, but there's just a mountain of data suggesting that mouse models of Alzheimer's and/or ABeta simply not that useful.
- rob_c 1y agoIf it's the removal of the proteins not the plaque I wonder if that's the cause of people chasing the plaque for years? Classic correlation causation problem if so... Time to go read
- CrazyStat 1y agoAmyloid plaques are protein.
- chc4 1y agoWasn't it revealed that the research supporting amyloid-beta plaque as the cause of Alzheimer's was fraudulent? https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease https://www.science.org/content/article/potential-fabricatio... https://www.science.org/content/article/alzheimer-s-scientist-resigns-after-university-finds-data-integrity-concerns-papers https://www.science.org/content/article/alzheimer-s-scientis...
- epgui 1y agoYes, in a sense... but that doesn't mean amyloid-beta is an irrelevant therapeutic target. It's a bit more complicated.
- jvanderbot 1y agoIIRC, it was revealed that treating this as a cause is wrong, it complicates or causes dementia, but is a symptom of something else, not a root cause of the disease. But treating symptoms, esp restoring cognitive function, is a good thing.
- p_j_w 1y agoI'm not a neuroscientist, but it seems that hypothesis existed before that paper and has more supporting evidence than what's been retracted: https://en.wikipedia.org/wiki/Biochemistry_of_Alzheimer%27s_disease#Amyloid_hypothesis https://en.wikipedia.org/wiki/Biochemistry_of_Alzheimer%27s_...
- mjamesaustin 1y agoThis therapy doesn't target the amyloid-beta plaques. It repairs the blood brain barrier, and then the body is able to clear away the plaques. Their buildup is a symptom of Alzheimers, not the cause. The problem with the amyloid-beta hypothesis was the assumption that these plaques were causing the Alzheimers and that removing them by itself could lead to a cure.
- lukeinator42 1y agoExactly this. Amyloid-beta plaques and their association with dementia were discovered early on (late 1800s/early 1900s https://en.wikipedia.org/wiki/Amyloid_plaques#History https://en.wikipedia.org/wiki/Amyloid_plaques#History), but the theory that they cause dementia hasn't panned out.
- btilly 1y agoYes, we have a mouse model of Alzheimer's that can be cured by preventing amyloid beta buildups. And billions of dollars in failed drug trials demonstrate that what works for those mice, doesn't work for humans. This has been demonstrated for many years. And yet we waste literally billions per year researching treatments that will only work in mice. And yet we regularly publish articles proclaiming that we can cure mice, humans are next! This research is BS and a waste of taxpayer money.
- jmount 1y agoIsn't it often even worse in that many of the "models" are intentionally inflicting a condition superficially similar to a symptom, and then showing some treatment blocks or reverses that? So sometimes nothing to do with the underlying disease.
- btilly 1y agoYes, this is exactly the problem with animal models. We can tell that the animal has the same symptoms. We don't know that it has it through the same pathway as humans. The models have worked often enough that it is reasonable to hope that what works in animals, will work in humans. And it is easier to experiment on animals. This is why they are used in research. But when what works in animals doesn't work in humans, repeatedly, we should stop using that animal model in research. Here are examples of treatments for Alzheimer's that worked in animals, reached human trials, then failed to help humans: AN1792 (active Aβ vaccine, Elan), Tarenflurbil (R-flurbiprofen), Semagacestat (γ-secretase inhibitor), Bapineuzumab (anti-Aβ mAb), Solanezumab (anti-Aβ mAb), Crenezumab, ponezumab, gantenerumab, and BACE inhibitors (e.g. verubecestat, atabecestat). All of these were considered promising enough in mice to be worth expensive human trials. Where they failed. Those weren't cheap failures, either.
- eli_gottlieb 1y agoYou've certainly got a point that if mice cannot and do not develop Alzheimer's naturally, we should use a model organism that can.
- alphazard 1y ago> Instead of targeting neurons directly, this method focuses on repairing the blood-brain barrier (BBB), the brain’s defence against harmful substances. By restoring proper BBB function, the researchers achieved a reversal of Alzheimer’s pathology in animal models. Alzheimer's patients often respond positively to exogenous ketone esthers, and a ketogenic diet. The proposed mechanism for this is that ketones are transported across the BBB differently than glucose. Even if glucose is unable to be transported into the brain, ketones often still are. Now that there is a drug to repair the BBB, and likely glucose transport as well, I expect the funding will mysteriously show up to properly investigate the "brain diabetes" theory of Alzheimers.
- GenerWork 1y ago>I expect the funding will mysteriously show up to properly investigate the "brain diabetes" theory of Alzheimers. There was the SNIFF [0] study that delivered insulin via nasal spray, so there's already some funding and studies happening. [0] https://www.clinicaltrials.gov/study/NCT01767909 https://www.clinicaltrials.gov/study/NCT01767909
- DANmode 1y agoGreat share, thanks.
- JumpCrisscross 1y ago> Now that there is a drug to repair the BBB (and likely glucose transport as well), I expect the funding will mysteriously show up to properly investigate the "brain diabetes" theory of Alzheimers Why is this cast as conspiracy versus a natural consequence of risk and incentives? (‘Brain diabetes’ is in no way a neglected avenue of Alzheimer’s research.)
- matthewdgreen 1y agoThere’s been a long-running Internet movement to cast the beta-amyloid and beta-amyloid/tau hypotheses as an evil plot by scientists to siphon money away from research that works. It’s a whole thing. I anssume it’s because Alzheimer’s legitimately sucks (my mom has it) and that means there has to be someone we can blame.
- 1970-01-01 1y agoWhy isn't "in mice" an automatic flag for posting? This is not a breakthrough in Alzheimer's nor is it headline news in Alzheimer's research.
- bookofjoe 1y agoI asked this question in Ask HN about six months ago but received little support and much criticism.
- eli_gottlieb 1y agoI emphatically support flagging all "medical" articles in which mice are the only species used as a disease model.
- inglor_cz 1y agoWhy should it be? Because of lacking relevance? The community can find even research in mice interesting - look just how much debate has this topic produced here. We're not an Alzheimers research forum, we are a bunch (tribe? murder?) of nerds who like to gab about new things. You'd have a better point if the "in mice" was hidden somewhere in the text - for subtle dishonesty, but as long as the title admits it openly, I don't see a reason to flag the submission in itself.
- DaveZale 1y agofrom the bbb wiki: There is also increasing evidence that a healthy gut microbiome is necessary to maintain BBB integrity, both in development and aging.[38][39][40][41] I'll drink to that (kefir)!
- stephenitis 1y agoCan you provide some linksv
- sys32768 1y agoI think the main progression is lymphatic dysfunction > chemical build-up > BBB damage > neurodegenerative plaques and tangles. My mother died from Alzheimer's at 77 but was the picture of health and happiness for many years prior, but never slept well to the point she had to have her own room away from Dad for many years. Maybe the trick is going to be repairing the BBB and stimulating lymphatic function rather than chasing down every factor that explains why the BBB and/or lymphatic function is compromised in the first place.
- JamesBarney 1y agoI think the cure is going to be something that dissolves tau tangles, or something safe enough we can give as a preventative to people 10-20 years before they develop symptoms that helps with amyloid.
- anon84873628 1y agoThe authors of this work believe the treatment enables BBB repair and restoration of healthy vasculature.
- BenFranklin100 1y agoPeople are criticizing mouse models of AD. There is understandable given the confusion of the roles of animals models in disease. Let me explain: First, the very name, ‘animal model of disease” is misnomer, and the cause of most of the confusion. Animal models are more accurately described as ‘models of mechanism’. Second, while mouse are different from humans and how a disease manifests is different as well, many of underlying mechanisms that drive a disease share strong similarities across species. Mice, rats, dogs, pigs, humans etc… all share the same fundamental building blocks and cellular/tissue/organ mechanisms. Studying how a disease or even partial aspects of a disease manifests in, say, a mouse, can offer extraordinary insights in how the disease may manifest in humans. This can provide a strong experimental basis for potential therapies in humans. (A rough analogy is the field of software is that different programs can use the same functions. Understanding how a function is misbehaving in a simple program can provide insights in how it is misbehaving in a more complex program.) Third, many diseases are difficult or impossible to study in humans. Alzheimer’s is a good example as the progression occurs on a timescale of decades. Further, we obviously can’t go around cutting out brain tissue from live humans. It’s a big topic, but hopefully my brief outline provides some context for the use of animals models. We scientists also use cell and organoid models, which, while lacking key details of animal models in unknown ways, can provide insights as well.
- dsign 1y agoIf the causal mechanism in Alzheimer's is not clear, what's to say it isn't about 20 or 20000 different things going wrong in ways and proportions which are very specific to each individual? I'm not criticizing basic research, which I consider immensely useful. Rather, the way we expect for it to become magical drugs. The peak of contradiction is posing that humans are inscrutable creations of God who wills us to age and die miserably, and in the same breath also wanting to have a neat repair handbook indicating fixed doses of the same drugs for each symptom--as if we were some cheap car model that comes without spares nor OBD port, and that it's only serviced at the end. I think we need to solve that.
- w10-1 1y ago> what's to say it isn't about 20 or 20000 different things going wrong In this case, the therapy resulted in old mice performing like young mice (in addition to the amyloid-beta level reducing).
- anon84873628 1y agoWell they synthesized a magic molecule that mimics an endogenous compound that stops functioning in the diseased systems. Everyone agrees with you. The whole era is "precision medicine".
- Rikudou 1y agoFor one hundredth goddamn time: Mice don't have Alzheimer's. They can't ever get it and almost none of the successes scientists achieve with the mice illness that has nothing to do with Alzheimer's except similar symptoms are reproducible in humans at all. I really wish the news sites would get it correctly from time to time, this is misleading as hell.
- gcanyon 1y ago> The researchers tested their approach in mice genetically programmed to overproduce Aβ and develop cognitive decline similar to Alzheimer’s pathology. Thoughts on that FTFA?
- rippeltippel 1y agoOriginal article was posted on HN: https://news.ycombinator.com/item?id=45508672 https://news.ycombinator.com/item?id=45508672
- amluto 1y agoThe original article is much better than this summary.
- chermi 1y agoThe headline really, really annoys me. It makes it sound causal, amyloid-B removal causes reversing symptoms of alzheimer's. Thus supporting and even making seem certain the still somehow overwhelmingly popular (not to sound like conspiracy anti-pharma guy(1)) amyloid theory of alzheimers. All this shows is that one of the effects of the treatment is clearing aggregates, IN MICE. That's it, nothing more. We don't know for sure the causal mechanism. There was/is a fanatical well-funded machine behind the amyloid hypothesis; that doesn't make it correct. There is much reason to doubt it or at least downgrade it to a contributing but not sole causal mechanism. (1) it is absolutely mind-boggling to me that the amyloid clearing drugs like Aduhelm got FDA approval while so many much more proven treatments for other diseases sit waiting.
- wewewedxfgdf 1y agoMice get all the big health discoveries. We're going to be ruled be a race of super healthy, immortal, super intelligent lab mice.
- jasonvorhe 1y agoNah, we just love torturing and killing animals for science.
- alehlopeh 1y agoI would personally torture a lot mice if it meant curing this disease.
- D-Coder 1y agoYou say that like it's a bad thing.
- DaveZale 1y agoFrom 2023: It has been suggested that the BBB breakdown may precede cognitive decline and neurodegeneration, highlighting the critical need for further exploration of the BBB’s role in AD and its potential as a therapeutic target [22]. The BBB endothelium is a specialized system of brain microvascular endothelial cells that separate circulating blood from the brain’s extracellular fluid, maintaining the brain’s homeostatic environment [23]. The BBB endothelium plays a crucial role in the protection and functioning of the brain, allowing the selective passage of nutrients and molecules essential for brain function while simultaneously preventing the entry of potentially neurotoxic substances [22]. Also interesting: the two-hit vascular hypothesis of AD suggests cerebrovascular damage (hit 1) as an initial insult that is self-sufficient to initiate neuronal injury and neurodegeneration. Additionally, it promotes the buildup of Alzheimer’s Aβ toxin in the brain (hit 2) https://pmc.ncbi.nlm.nih.gov/articles/PMC10671257/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10671257/
- inglor_cz 1y agoSo, yet another experiment that points to vascularization problems as the root cause of dementia. You know what? Some studies (not all) have shown association of Viagra use with a reduced risk of Alzheimer's. That would fit into the picture. Viagra was originally intended to treat high blood pressure and heart disease.
- tim333 1y ago"reversing Alzheimer’s in mice" is a bit of a clickbait stretch. Treatments in humans targeting amyloid have failed to have much effect on Alzheimer's.