Novel dementia vaccine on track for human trials within two years:
A newly published study has described the successful results in mice of a novel vaccine designed to prevent neurodegeneration associated with Alzheimer's disease. The researchers suggest this "dementia vaccine" is now ready for human trials, and if successful could become the "breakthrough of the next decade."
The new study, led by the Institute for Molecular Medicine and University of California, Irvine, describes the effect of a vaccine designed to generate antibodies that both prevent, and remove, the aggregation of amyloid and tau proteins in the brain. The accumulation of these two proteins is thought to be the primary pathological cause of neurodegeneration associated with Alzheimer's disease.
The research revealed the vaccine led to significant decreases in both tau and amyloid accumulation in the brains of bigenic mice engineered to exhibit aggregations of these toxic proteins. Many prior failed Alzheimer's treatments over the past few years have focused individually on either amyloid or tau protein reductions, but growing evidence suggests a synergistic relationship between the two toxic proteins may be driving neurodegeneration. Hence the hypothesis a combination therapy may be the most effective way to prevent this kind of dementia.
This new treatment combines two vaccines, dubbed AV-1959R and AV-1980R, which are designed to respectively target amyloid and tau protein aggregations. The vaccine is formulated in a novel adjuvant called Advax, developed by a team of Australian researchers to enhance vaccine immunogenicity.
Advax has been developed by Nikolai Petrovsky, a scientist from Australia's Flinders University who told ABC News Australia the new formulation offers the potential to act as both a preventative vaccine against the development of neurodegeneration, and a curative treatment in subjects already suffering from a build-up of these toxic proteins.
[...] The new research was published in the journal Alzheimer's Research & Therapy.
Related Stories
An Alzheimer's Nasal Spray Vaccine Is About to Enter Human Trials For The First Time
Alzheimer's treatments seemed like an unlikely prospect mere months ago.
Drug trials tried and failed for 20 years to produce treatments that would stop the progression of the disease, and several large pharmaceutical companies abandoned the mission of developing Alzheimer's treatments altogether.
[...] Now, the field of Alzheimer's treatments may finally be opening up.
Last week, Brigham and Women's Hospital announced it would spearhead the first human trial of a nasal vaccine for Alzheimer's, designed to prevent or slow the disease's progression.
The trial is small – 16 people between ages 60 to 85 with Alzheimer's symptoms will receive two doses of the vaccine one week apart. But it builds on decades of research suggesting that stimulating the immune system can help clear out beta-amyloid plaques in the brain.
[...] The vaccine sprays a drug called Protollin directly into the nasal passage, with the goal of activating immune cells to remove the plaque.
FDA OKs Phase 1 Trial of Nasal Spray Immunotherapy Protollin
Protollin is a new intranasal immunotherapy made of proteins derived from the outer membrane of certain bacteria. It works by stimulating the innate immune system — the part of the immune system that serves as the body's first line of defense — to clear amyloid-beta plaques and tau tangles from the brain.
It worked in mice, so it must be good.
Also at Medical News Today.
Related: Novel Dementia Vaccine on Track for Human Trials Within Two Years
(Score: -1, Offtopic) by Anonymous Coward on Monday January 06 2020, @12:40PM
While this development might be completely legit...
Don't forget that inside trader Chris Collins was on the board of Australian-based firm Innate Immunotherapeutics--which sure looked like a pump and dump operation (looking from the sidelines--I live in Collins' district, but didn't vote for him).
(Score: 3, Interesting) by nishi.b on Monday January 06 2020, @12:46PM (21 children)
Very interesting, but past experiments failed and it was hypothesized that the proteins that are targetted here may be a consequence of the disease process and not a cause of it. So time will tell whether this will clear the proteins in patients while still having a progressing disease or whether it really stops the disease.
(Score: 4, Interesting) by RS3 on Monday January 06 2020, @02:22PM (19 children)
That was my reaction too, but FTS:
"both tau and amyloid accumulation in the brains" AND "growing evidence suggests a synergistic relationship between the two toxic proteins may be driving neurodegeneration."
Time and more testing will tell. Even if it doesn't work, medical science will have learned something. Either way, these people have no other hope, so why not try something, as long as it doesn't make them worse of course.
(Score: 0) by Anonymous Coward on Monday January 06 2020, @03:09PM (8 children)
No, they will apparently never learn to stop targeting amyloid beta. From the beginning it was a very weak correlation with questionable cause and effect. Today, it is a very weak correlation with questionable cause and effect and a circular definition.
30% of people without alzheimers symptoms have elevated amyloid beta. 30% of people with those symptoms have elevated amyloid beta. By definition, those people have Alzheimer's.
Amyloids are the most thermodynamic my favorable state for peptides to be in, any sort of disfunction will lead to their accumulation. That is why you find them elevated in every single diseased tissue ever checked. Just like oxidative stress.
It is apparently impossible for medical researchers to accept that the amyloid hypothesis became dogma based on nothing. No trial for anything targeting amyloid beta has ever shown promise, which leads me to believe it must even be protective in some way, by now at least one drug should have been approved randomly.
The previous acetylcholine hypothesis has more going for it and actually did lead to apparently useful treatments. Why was it replaced with this clearly false amyloid hypothesis which is apparently impossible to eradicate?
(Score: 2) by RS3 on Monday January 06 2020, @03:42PM (7 children)
In other words, my favorite cynicism: "popular misconception".
(Score: 0) by Anonymous Coward on Monday January 06 2020, @03:54PM (6 children)
It is worse than just a misconception. The amyloid beta saga is the most unscientific thing going on in medicine. The understanding of disease has actually been regressing because of it.
It is a step backward from the previous acetylcholine hypothesis, and I've never seen any explanation for why/how it became dogma.
(Score: 2) by RS3 on Monday January 06 2020, @04:27PM (5 children)
"Popular misconception" has a deeper meaning. I think you're the same AC person I've exchanged posts with here before, and you're quite literal, if that's the correct word, with word meanings. And that's okay, but there are often deeper meanings and implications.
For there to be a "popular misconception", you need people who are somewhat sheep-like, in that they will believe and glom onto some fad. There's another term for it that I forget, but it describes the concept of a fad, or something "viral"- people pile on without really thinking. Everyone is in such a race to be the first to discover something that they don't have time to deeply evaluate. I don't blame the individuals as much as I blame the whole system (of competition, rewards for being the first to the finish line, etc.) Not sure how to fix it, but something that rewards group collaboration more might help. But some people have a disproportionate share of ego, so maybe it's unfixable.
I remember reading about the amyloid beta deposits, and my first thought was "They're likely the waste product of the damage mechanism; I wonder what's causing them?" (prions?...)
(Score: 1, Insightful) by Anonymous Coward on Monday January 06 2020, @04:53PM (4 children)
It is more like when someone gets too sick to take out the trash, so it will accumulate in their house over time. Of course, accumulated trash can also be its own source of illness.
(Score: 2) by RS3 on Monday January 06 2020, @05:34PM (3 children)
Interesting analogy. No proof that it would be the same situation inside a brain, but maybe tau and amyloid beta are prion fertilizer?
(Score: 1, Informative) by Anonymous Coward on Monday January 06 2020, @05:53PM (2 children)
Prions and amyloids are the same thing.
(Score: 2) by RS3 on Monday January 06 2020, @09:29PM (1 child)
Egads! I need to do my research... too busy with legal research right now... and normal tech work. would rather work in healthcare / medical / research...
(Score: 0) by Anonymous Coward on Monday January 06 2020, @09:40PM
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601216/ [nih.gov]
(Score: 0) by Anonymous Coward on Monday January 06 2020, @03:17PM (9 children)
If you want to give them hope, give them vitamin c which is the least toxic substance known to man (less toxic than water) and the best antioxidant in the universe and known to be depleted in alzhiemers patients.
In fact, if hospitals would end their bizarre policy of not routinely checking vitamin c levels they will find almost everyone who is sick have lower levels and need much more vitamin c than healthy people to get them back to normal (because it gets consumed faster in the diseased tissue).
(Score: 0) by Anonymous Coward on Monday January 06 2020, @03:27PM (8 children)
Your vitamin C theories were debunked decades ago.
Plus you’ve been dead for a quarter century. Get off the internet already!
(Score: 0) by Anonymous Coward on Monday January 06 2020, @03:35PM (5 children)
The only debunkings are for giving people extremely low infrequent doses. If your body needs 10 grams every two hours but you give 100 mg per day, why would you expect anything to happen?
It's like debunking the idea water cures thirst because people are still thirsty after taking one sip.
(Score: 2) by RS3 on Monday January 06 2020, @04:12PM (4 children)
Perhaps Vit. C only works well in some people, for some diseases?
(Score: 0) by Anonymous Coward on Monday January 06 2020, @04:28PM
Its primary function is not as a vitamin, it is as an antioxidant. It will be helpful anytime too much inflammation is a problem (which is almost every disease). In most cases it seems to reduce symptoms, sometimes to zero, instead of curing anything.
(Score: 1, Informative) by Anonymous Coward on Monday January 06 2020, @04:39PM (2 children)
Also, the dose required is individualized and seems to depends on your current state of health. This has been independently noticed twice that I know of. Once by Russel Jaffe:
https://i.ibb.co/B2cCcfw/jaffe1.png [i.ibb.co]
https://i.ibb.co/3MxX81T/jaffe2.png [i.ibb.co]
And once by Robert Cathcart:
https://www.ncbi.nlm.nih.gov/pubmed/7321921 [nih.gov]
So a clinical trial that gives everyone the same dose, or dose according to weight/etc is not going to work. The dose must depend on the redox state of your body.
(Score: 2) by RS3 on Monday January 06 2020, @05:52PM (1 child)
Very interesting, thank you. I didn't realize Vit. C helps with inflammation.
So how to treat someone who is quite ill, already has very loose stool, scurvy and other vit. C deficiency symptoms? Maybe IV vit. C?
(Score: 0) by Anonymous Coward on Monday January 06 2020, @06:16PM
The IV vitamin c is going to be more expensive just due to the IV. First just get sodium ascorbate or ascorbic acid powder and see how much your body will absorb and how you feel. Just look up ascorbate cleanse, titrating to bowel tolerance, etc.
(Score: 0) by Anonymous Coward on Monday January 06 2020, @03:44PM (1 child)
Imagine there is a forest fire but you have no way of dumping water on any one part of the forest, you can only dump water over the entire forest. Then you are going to need to use way more water to get the required amount to the actual fire. Most of it will appear to be wasted, but it was necessary to stop the fire.
Fire = oxidative stress
Water = vitamin c
(Score: 0) by Anonymous Coward on Monday January 06 2020, @04:18PM
So we should use fire to burn out the tau and amyloid beta? This is so confusing...
(Score: 1, Interesting) by Anonymous Coward on Monday January 06 2020, @09:38PM
Alzheimer's disease is associated with herpes. The proteins may be there to keep the virus from spreading. Removing the protein might cause a raging case of cerebral herpes.
Interestingly enough, neurons involved in memory sometimes transmit RNA to each other via capsules that resemble viruses. It seems that the body has repurposed viral DNA in the genome. It wouldn't be surprising that a mechanism to stop viral transmission in brain tissue would interfere with memory.
(Score: 0) by Anonymous Coward on Monday January 06 2020, @02:12PM (11 children)
Previous failed treatments demonstrated, a number of times, that working against the amyloid makes the disease *worse*. It seems the underlying cause (neiroinfection or whatever it is, opinions still are divided as of 2019) is the problem, and not the brain's biochemical reaction to it.
And still, here they go again wasting money and uselessly murdering mice (and likely some humans too, when human trials come; an autoimmune reaction inside the brain is not a thing to wish on anyone, enemy or friend).
(Score: 2) by RS3 on Monday January 06 2020, @02:26PM (10 children)
Very good points, if you're correct.
> working against the amyloid makes the disease *worse*
Any links to these findings?
(Score: 2) by HiThere on Monday January 06 2020, @05:07PM (8 children)
Well, there *are* lots of prior results that focus on the amyloid plaques which failed. So I don't give this one a high probability. And mouse models don't seem to accurately model the human disease.
OTOH, it's probably better than just throwing up our hands and saying "we don't know what to try". The immune system is complex, and maybe this will work. I just wouldn't put any money or much hope behind it.
Javascript is what you use to allow unknown third parties to run software you have no idea about on your computer.
(Score: 0) by Anonymous Coward on Monday January 06 2020, @05:14PM (7 children)
Why is this always presented as the alternative? The alternative isn't nothing, it is the cholinergic hypothesis, which has already resulted in useful drugs. For no apparent reason this was replaced by the amyloid hypothesis, which has resulted in nothing.
There may be an even better idea than the cholinergic hypothesis out there too.
(Score: 0) by Anonymous Coward on Monday January 06 2020, @10:57PM (6 children)
That is not the only alternative either, although it is the oldest. The reason that it was replaced is because cholinesterase and acetylcholinesterase inhibitors only improve the symptoms of the disease while the signs, especially those in the brain structure, continue to worsen. In addition, they don't always decrease the symptoms of AD despite all of them increasing the levels of the neurotransmitter. Both of those suggest that you are looking at an effect of the disease, rather than a cause.
(Score: 0) by Anonymous Coward on Tuesday January 07 2020, @12:34AM (5 children)
Yes, but it was replaced with a new theory that does not work at all... Shouldnt there be some sort of evidential threshold a new theory must surpass before it becomes dogma?
Interesting idea -> dogma is not science.
(Score: 0) by Anonymous Coward on Tuesday January 07 2020, @02:14AM (4 children)
There are other hypotheses out there. I was just pointing out that the one you offered has been mostly ruled out, and how that is similar to how the amyloid hypothesis is showing problems with its theoretical causal models. But at the time, it made sense given what they were seeing in the brain and the previously niche prion diseases coming to wider attention. Part of the problem, which some research is bearing out, may be that "Alzheimer's Disease" is actually multiple diseases with similar clinical features. Just as NFTs and enlarged ventricles are known to be involved with other diseases, the symptoms and signs of AD might be a syndrome indicative of multiple diseases.
For example, a large chunk of AD is hereditary through multiple genes with different proposed links (see DNS-APP studies and EOAD). There is also the idea that it is some sort of inflammatory process of the brain, either through injury or infection. It could be a failure of the BBB or caused by lead exposure or autoimmune based or retrogenesis or even more. Or, as mentioned, all of the above.
The real problem is how people donate money. The big donors all do it to particular doctors, research hospitals, or other big donors. Of course they use it to do the research they've been doing or what looks most fruitful at the time. It is the smaller grant or University research that will explore alternate ideas because they aren't flush with cash to compete along the same lines.
(Score: 0) by Anonymous Coward on Tuesday January 07 2020, @06:41AM (3 children)
It made sense to investigate it, not elevate it to dogma. This was done based on nothing.
Ah, the "it is so complicated we need to call it multiple diseases canard" first invented by the failed war on cancer people. Cancer is one disease characterized by cells undergoing inappropriate division, chromosomal instability, high iron content, and oxidative stress. Instead of targeting those things they have been targeting specific genes that the cell lines will simply mutate to resistance. That is why they failed.
When you study something for decades spending hundreds of billions of dollars and in the end things seem more complicated than you started with, something is seriously wrong with what you are doing.
The goal of science is to discover general rules/laws by which a phenomenon operates. Perhaps biomed researchers should use research methods appropriate to that goal instead of checking whether two groups are *different* over and over and then they wont have to come up with excuses like this.
https://www.cell.com/cancer-cell/fulltext/S1535-6108(02)00133-2 [cell.com]
(Score: 0) by Anonymous Coward on Tuesday January 07 2020, @06:49AM
Looks like cancer research stagnated about 15 years before amyloid research did.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835886/ [nih.gov]
(Score: 0) by Anonymous Coward on Tuesday January 07 2020, @09:42PM (1 child)
Like medicine or anything else in general? Just look at Newton's ideas vs Einstein's general relativity. They explain the same phenomenon, but the latter is more complicated than the former. Or medicine, first it was spirits, then we discovered the germ theory of disease, then we discovered different kinds of germs, then we discovered that not all germs cause disease the same way, and we learned that the same germ can cause multiple diseases. That stuffy nose you have? Back in the day, you either had an evil spirit or were outside in the cold too long, now we know that it could be any number of viral, fungal, or bacterial infections, allergies, inflammatory disorders, anatomical problems, and more. But I guess that can't be true because science is supposed to be simple and there should only be one disease there.
Same with cancer. It is a group of diseases because there are many different genetic changes that cause cells to become cancerous. In addition, not all changes will cause cancers in all types of cells. The treatments also have to differ depending on the type of cancerous cells because they don't all react the same way to the same treatments. But if you want a simple rule, without the "right combination" genes, you don't get cancer, a point driven home by comparative oncology. Any wonder why they focus on the underlying genetic factors, especially in a preventative role in addition to apoptosis and immunotherapy?
And medical and biomedical researchers use all the testing they have. There is in vitro testing, in vivo animal models, and even human experimentation. The problem is that, unlike many fields of research, medical research is ethically limited. There is limited ability to expose people to treatments, pathogens, or environments, to chop people up or biopsy their tissues, and to do many things even with their consent. Heck, you even have to get permission from an ethics board to ask them questions that are personally identifiable or beyond symptom presentation.
I understand the desire to make things simple, but sometimes things are complex. The previously mentioned sinusitis, weak interaction requiring 3 types of bosons, supply and demand depends on expectation, weather, oxygen theory of combustion, wave-particle duality? All of that is too complicated compared to the alternatives, must be wrong. Lets just undo modern science in the search of your simplicity.
(Score: 0) by Anonymous Coward on Tuesday January 07 2020, @11:15PM
Sorry, you are totally naive. Show me one mainstream medical "theory" that even tries to make a precise prediction like Newton and Einstein. Most of them don't even know how to do calculus or program their ideas into a computational model. It is systematic incompetence and it shows. There has been no real progress in cancer, dementia, strokes, TBI, etc for decades. And the little progress we have seen came from "crackpots" like Kary Mullis and Raymond Damadian.
(Score: 1, Informative) by Anonymous Coward on Monday January 06 2020, @05:52PM
>Any links to these findings?
https://www.medpagetoday.com/meetingcoverage/aaic/52705 [medpagetoday.com]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693547/ [nih.gov]
And meanwhile https://alzres.biomedcentral.com/articles/10.1186/alzrt269 [biomedcentral.com] :
"Most disease-modifying trials have some form of Aβ protein as the pharmacologic target (that is, four of six current Phase 3 compounds of disease-modifying agents target the amyloid-beta protein). One-hundred forty-five (65.6%) of 221 trials of disease-modifying agents registered in the 2002 through 2012 period were directed at this target. The target is unvalidated, and no class of agents has shown efficacy for this target in human clinical trials. Many animal models of amyloidosis have shown biological and behavioral benefit from anti-Aβ agents, creating a “translational gap” between human and animal studies [27–30]."
"The definition of insanity is doing the same thing over and over again and expecting a different result."
P.S.: If https://doi.org/10.1016/j.neuron.2018.06.030 [doi.org] is correct in that, the Aβ protein serves a *defensive* role against the underlying infection. End results of a treatment designed to remove it, are easy to deduce if that is the case.
(Score: 2) by JoeMerchant on Monday January 06 2020, @04:15PM
If the stimulated antibodies are targeting amyloid and tau protein plaques, isn't that like calling a crystal growing factory a farming operation?
Україна досі не є частиною Росії Слава Україні🌻 https://news.stanford.edu/2023/02/17/will-russia-ukraine-war-end