8 ms·
Alzheimer’s Drug Failure Leaves Scientists Seeking New Direction
- neonate 8y agohttps://outline.com/rfdTx9 https://outline.com/rfdTx9
- melling 8y agoHealthcare costs for Alzheimer’s is going to be astronomical. https://www.alzheimers.net/research-spending-vs-annual-care-costs/ https://www.alzheimers.net/research-spending-vs-annual-care-... Finding a cure or delaying symptoms by a decade would save a lot of money. Let’s add $10 billion to the federal research budget and add a motivated czar to oversee the research. Wonder if Bill Gates has a few extra cycles.
- Retric 8y agoI don’t know if any drug could actually cure Alzheimer’s. We know we can’t completely replace exercise with a drug because mechanical stress is part of the process. So, drugs might work on Alzheimer’s patients, but without knowing the cause it’s still up in the air.
- Brakenshire 8y agoEven if there was only a one in ten chance, it justifies an enormous research budget, when the costs are $200bn a year in the US alone. What we’re actually spending is far too little.
- Retric 8y ago10% chance in the next 50 years seems extremely optimistic. We have no idea if it’s caused by a pathogen or something else, or even if it’s a single disease or several related diseases.
- melling 8y agoNo one said all the money would be spent on drug research. The idea is that some basic science would also be done.
- Retric 8y agoOutside of basic research there is little to be done. We don’t have a good animal model, and human testing on a disease that takes 30+ years is almost hopeless without a much better understanding of what’s going on.
- melling 8y agoI'm not exactly sure what your point is? You're trying to tell me how hard the problem is? I never said the problem was easy, never offered a solution, or claimed there's a clear path to a solution. Alzheimer's is an underfunded disease given the amount that it costs us in healthcare. I'm saying we should spend a lot more money and put someone in charge of the money who will spend it effectively.
- Retric 8y agoSaying it’s underfunded makes assumptions around how likely we are to find a solution. If hypothetically spending 1 trillion dollars gives us a 1 in 1 Billion chance of finding a cure then that’s simply not worth it. Further spending more money does not give linear increases in value. Bumping up from around 2 bullion a year sounds great from a budget standpoint, but do we have another 8 Billion dollars worth of promising research to do next year and people able to carry that out? We are already ramping up funding rapidly, but there are only so many specialists out there.
- melling 8y agoWe don't need a cure for the investment to pay off. If we can simply slow the disease, we'll save a fortune. If the disease takes an additional decade, that's a lot of healthcare costs. You might even die from something else before it gets worse. I never claimed that if we doubled the money, we'd get double the research. I simply threw out a SMALL number like $10 billion a year. We spend $28 billion on HIV, for example. https://www.hiv.gov/federal-response/funding/budget https://www.hiv.gov/federal-response/funding/budget I've read lots of articles over the decades about how AIDS would never be cured. Now you can live a long productive life with the disease.
- buboard 8y agoPresuming Bill Gates has track record in finding cures?
- corndoge 8y agoB&MGF were largely responsible for the eradication of polio
- layoutIfNeeded 8y ago*in the developing world Polio have been eradicated in developed nations by the 1980s.
- shim2k 8y agoWell, to be fair his comment is still correct.
- BurningFrog 8y agoEven Bill Gates can't eradicate polio where it doesn't exist!
- melling 8y agoHe needs to figure out where to effectively invest the money. He's already investing some of his money. https://www.forbes.com/sites/denizcam/2017/11/13/microsoft-billionaire-bill-gates-is-investing-100-million-in-alzheimers-research/#3520899b328f https://www.forbes.com/sites/denizcam/2017/11/13/microsoft-b...
- ineedasername 8y agoBill Gates, with the B&MGF, has a decent track record of finding and boosting low-cost solutions to chronic and systemic issues. Basically, choosing where to focus resources to the best effect. I'm not saying he'd revolutionize this field, but there are worse choices than someone with his track record.
- 8y ago
- Bluestrike2 8y agoThe Alzheimer's Association's 2018 annual report[0] estimates total healthcare expenditures at $277 billion per year in 2018 alone. That's in addition to the $232 billion cost of ~18.4 billion hours of care by family and unpaid caregivers which itself excludes the immediate expenditures associated with that care, the effects of decline in mental and physical health of the caregivers themselves, changes in workplace participation resulting from providing said caregiving, etc. Or the myriad of other costs, many of which are indirect. Even miniscule increases in R&D funding for Alzheimer's could lead to a truly massive ROI for society. 0. https://www.alz.org/media/HomeOffice/Facts%20and%20Figures/facts-and-figures.pdf https://www.alz.org/media/HomeOffice/Facts%20and%20Figures/f...
- antiviral 8y agoWhat if the presence of beta amyloid is not the cause of Alzheimer’s but rather the symptom? In that case, these drugs should be ineffective. It would be interesting to see how brain function continues to be impaired even while the beta amyloids are suppressed using these drugs, helping us get to the real process.
- dpatrick86 8y agoWhat if it's both?
- ops4c0d3 8y agoFor those willing (or those with power of attorney), would nanoparticle research experiments be worth the wont, per OP's point? While two major drug trials are being dropped towards the amyloid target (based on aducanumab) on public display, why not look towards AI and neuroplasticity measures to find the next set of targets
- jnurmine 8y agoDisclaimer: I am not a doctor, just try to follow up on big things impacting many people. According to my understanding of the amyloid cascade hypothesis, the amyloid beta accumulation is not a cause but indeed a symptom (of gene mutations/something). Then, the amyloid beta basically clumps up and other mechanisms happen and neurons get damaged and this collective damage is known as Alzheimer's Disease. So the amyloid beta is just one link in the chain. Even with a complete removal of that link (removing/reducing amyloid beta), one cannot expect the disease to be reversed, since removal of something in-between does not revert the already occured damage. But accumulation of new damage might slow down. Coupled with improved early detection even this would be very helpful to many people. As far as I know, some modest slowing down was observed in some of the clinical trials. This could mean the amyloid cascade hypothesis isn't completely wrong. Now, what I found really, really interesting is that first Biogen gets ca. 20 % of its market value vaporized after the aducanumab (a joint venture betwen Biogen and Eisai). This is nearly 20 billion USD. Then, Eisai informs that they still go forward with another substance called BAN2401. The BAN2401 also targets amyloid beta, but in a different way than others (protofibrils). So... I'm thinking here that this is either a genius move or a really dumb one. It cannot really be anything in-between. I honestly hope it'll be a genius move.
- fasteo 8y agoOne alternative theory: Alzheimer as a metabolic disease. "We conclude that the term “type 3 diabetes” accurately reflects the fact that AD represents a form of diabetes that selectively involves the brain and has molecular and biochemical features that overlap with both type 1 diabetes mellitus and T2DM." [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/
- pjkundert 8y agoSignificant impact in 30 days. Without changing diet to reduce glucose. Can’t achieve 1mmol/L of Ketones in the blood, though, without a Ketogenic diet. The brain lights up in the PET scan on a Ketogenic diet: https://youtu.be/OU26epaihmw?t=1469 https://youtu.be/OU26epaihmw?t=1469
- mft_ 8y agoWasn't that PET scan showing ketone uptake? So it showed that brains can use ketones... but nothing about the activity or ability of the brain otherwise?
- copperx 8y agoYes. I have no idea what OP assumed by "the brain lights up."
- pjkundert 8y agoThe researcher claimed to have observed declining energy use for years before symptoms occurred, showing decreasing energy consumption leading to cell death regardless of fuel availability, finally leading to Alzheimer’s symptoms. Provision of ketones alone reversed this energy starvation. The PET scan literally lit up like a Christmas tree — turned from all blue/black to red! It was near the end of the presentation... If neural cellular degeneration is the target of any Alzheimer’s management strategy, wouldn’t dramatic energy consumption declines over decades before cell death, and reversal of these declines after a short treatment be of specific interest?
- kobieyc 8y agoThis book https://www.amazon.com/dp/0735216207 https://www.amazon.com/dp/0735216207
- JPLeRouzic 8y agoI read it, it is interesting but it tells only a way to mitigate the disease, not to cure it. And I would love if there were independent studies that could confirm Bredesen's writings (I do not say there are none, just that I am not aware of them).
- dawhizkid 8y agoI'm taking every preventative measure I can at a young age to reduce chance of Alzheimer's later in life, starting with low carb intake (+ no sugar) and IF. I can't think of anything more depressing than working your whole life so you can retire only to go into retirement and be diagnosed with Alzheimer's.
- ams6110 8y agoNews flash: we're all going to die, and time flies. At the typical retirement age of 65, most people have 10 or 15 years left. I'd advise a sensible diet and enjoying life while you are young. Don't spend time ruminating about what might kill you when you're near the end of your life regardless.
- AQuantized 8y agoLife expectancy is around 20 years at 65 in most developed countries.
- ams6110 8y agoFine. Point being, 20 years sounds like a long time when you're 25. When you're 55 or 60, and reflect on how fast that time went by, 15 or 20 years doesn't sound like very long. Certainly not enough time to make up for a lifetime of denying yourself life's pleasures thinking you're going to make up for it when you're old. Edit to add: none of us are guaranteed anything. You could get cancer and be dead at 40. Or younger. Avoiding reckless risks is one thing. Thinking you really have much control over diseases you might get in 40 years from now is another.
- nobodyandproud 8y agoThere's a novel theory that herpes is the culprit for a significant number of Alzheimer's patients. This line of thought was originally discounted, under the (mistaken) belief that the blood/brain barrier made this impossible.
- AlexCoventry 8y agoWhat's the evidence?
- hackandtrip 8y ago(I'm not an expert) Isn't this evidence correlated to the presence of beta-amyloid in the brain and the increased time required to clean them with herpes? As far as I read it, the evidence that beta-amyloid are a cause and not the consequence of Alz is not there. Also, I think that making such a statement for institutions needs solids theory, because it could effect a major part of population
- nabla9 8y agoI think more money should be directed towards tools, sensors and technology that can be used so map and study brain and biochemistry in general, and not just particular pathologies. Expansion microscopy, optogenetics and deep brain stimulation via temporally interfering electric fields are good examples of that. The surprising result that you can clear amyloids from the brain (only in transgenic mice) with 40 Hz light therapy is good example of surprising findings you get when you build new tools.
- dcbadacd 8y ago"I'm going for my biannual brain plaque checkup" will be a sentence I won't be surprised hearing. I think it's just a matter of time when we figure out brains need a bit of human-assisted maintenance just like teeth.
- ineedasername 8y agoI'm surprised that a range of existing drugs with neuroprotective capabilities haven't received more attention. The cynic in me says it's because many of them are cheap generics that have little financial upside for large pharmaceuticals. As an example, a range of anticonvulsant drugs exhibit neuroprotective effects. Depakote appears to be the best studief of the lot for this, but that's not saying much.Something like lamotrogine has similar results with lower side effect profile. These are widely used drugs for diseases like epilepsy, but they are also used for a wide range of mental health diseases where psychosis and dementia are issues because they are very effective in those areas as well. A nice bonus in treating another disease with similar neuro symptoms. This probably wouldn't be front-line treatment, but alongside amyloid reducing medications could form a powerful combination. The biggest obstacle might be the side effects, but judicial use in the earliest stages or in high risk poulations would probably be useful. The problem is right now the data is limited to very small studies or anecdotal case studies of individual patients that were treated off label.
- radicalbyte 8y ago> The cynic in me says it's because many > of them are cheap generics that have > little financial upside for large > pharmaceuticals. The patent is for problem + solution. You can patent many solutions for one problem and also a solution for many problems. If they prove, say, that vitamin C stops Alzheimer's then they can patent it for that usage. You see this a lot in cancer treatment and it makes a lot of sense. In a proper functioning system (i.e. not the USA±) it's a pretty decent solution. ± Seriously, the system there is designed so all in theory competing components are incentivized to work against consumer interests. Same thing with the housing market pushing house prices (5% interest on 500k is more $ then 5% on 200k, house sellers/older owners think they're rich but only benefit when they sell and downsize; only winners are lenders and real estate investors).
- busyant 8y ago> If they prove, say, that vitamin C stops Alzheimer's then they can patent it for that usage. Here is an article discussing this approach: http://stm.sciencemag.org/content/6/248/248fs30 http://stm.sciencemag.org/content/6/248/248fs30 I call them "use patents" but I am not sure if that is an official term or just a colloquialism.
- djsumdog 8y agoCould alzheimer's be more like cancer, where there are several variants and several causes? It seems like beta amyloid were looked at because they produce similar protein manifolding to prions. Other comments on here mention herpes (which is incredibly common. I've never had cold-sores, but dated enough people who have where I may just have it and not present, and it can't easily be tested for since it produced very similar antibodies to chickenpox).
- hunta2097 8y agoI think this may be the case for many brain-related illnesses. My son is severely autistic and through schools etc I know a lot of autistic children and adults. They are all very different but still labelled as "autistic spectrum". I think there are many causes with many similar symptoms, which is why no-one has discovered a common cause.
- mattkrause 8y agoThis is definitely true for autism. It’s clearly somewhat heritable, but no one has found a gene or mutation that all people with autism share. Study A picks out this gene from one set of families, Study B picks out a totally different gene (and can’t replicate A’s findings). Alzheimer’s is a little odd in that most (maybe all) patients seem to have the plaques. Removing the plaques seems to do nothing though so it might be a side effect of something else going wrong.
- Gibbon1 8y agoThat's my opinion have a special needs brother. I'm down on the side that these are mostly subtle developmental disorders. Both structural and in neural 'presets'. The latter I think explains kids with specific deficits that disappear over time.
- tonetheman 8y agoI watched two people get it side by side... It felt like I was watching them catch a cold. It is only anecdotal but it feels like it was a virus or something catching.
- fraggle222 8y agoBrush your teeth (and gums): https://www.perio.org/consumer/alzheimers-and-periodontal-disease https://www.perio.org/consumer/alzheimers-and-periodontal-di...
- graeme 8y agoRead an interesting anecdote on amyloids in Why We Sleep. During a certain sleep phase, the brain tissues change size and open up pathways for cerebrospinal fluid to pass this. This washes out amyloids. Over time with age and with brain damage, older adults lose the ability to generate this type of sleep, and so there is less cleaning. Does anyone know any more about this? It seems plausible that the cause could be partly due to a loss of this sleep cleaning function. Indeed lack of sleep is correlated with alzheimers. But that's just a book anecdote. I'd be curious to read more.
- holowire 8y agoI am currently reading Why We Sleep as well, and Matthew Walker's research on the topic is really interesting to consider within the larger constellation of approaches to Alzheimer's—particularly in context of the dietary/metabolic angle. The neural maintenance that occurs during sleep, the body's circadian mechanisms and quality of diet all seem to be highly complementary and ultimately point towards a more holistic and fundamental understanding of the disease (or brain physiology in general). It's been demonstrated pretty comprehensively that quality of diet and timing of eating have a profound effect on how well the body functions as a whole, so the sleep component seems to be an important thread in tying all of these approaches together.
- mrnobody_67 8y agoUltrasound to break up plaques in the brain: https://www.fusfoundation.org/diseases-and-conditions/neurological/alzheimers-disease https://www.fusfoundation.org/diseases-and-conditions/neurol...
- ncmncm 8y agoThe present generation of Alzheimer's researchers has a big, big problem. The best evidence now points to infection as the cause, but they are not infectious-disease specialists. It takes a long, long time to become an infectious-disease specialist, and there are lots already. What will they do when it turns out they have none of the skills needed to advance the study and treatment of Alzheimer's? The present generation of Alzheimer's patients has a big problem, too. Grants for research into Alzheimer's are controlled by the present generation of researchers, who have no particular desire to learn that Alzheimer's is an infectious disease. So, negligible work is going into establishing an infectious-disease etiology, never mind effective treatment. Publications supporting an infectious-disease cause of Alzheimer's are, likewise, not especially welcomed by established Alzheimer's referees. The herpes-family observations go back twenty years, and are only now gaining traction. The gingivalis observations are more recent. This is an area where one wealthy donor could make an enormous difference that might improve the lives of millions in a very short time.
- cma 8y agoIsn't there a lot of crossover with infectious disease research due to prion disease similarities?
- est31 8y agoScience has always had the problem of the establishment fighting new theories/insights. Max Planck once said: > A new scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it. Science has been able to deal with this problem for a long time.
- ncmncm 8y agoHalting progress for several decades, and blighting the careers of its best people until the old guard dies is not "dealing with it". That is actively failing to deal with it.
- homieg33 8y agoI’m not sure the best evidence for AD is infectious. Do you have sources? Mutations in the APP (amyloid precursor protein), PSEN1, and PSEN2 genes are shown to cause early onset AD with very high penetrance. Here’s an overview of AD genetics: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044597/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044597/ One interesting comment from this article: “...which subsequently led to the cloning of the APP type I integral membrane glycoprotein from which Aβ is proteolytically derived. The APP gene was then mapped to chromosome 21q, which accounted for the observation that patients with Down syndrome (trisomy 21) develop amyloid deposits and the neuropathological features of AD when in their 40s”