1229 replies to this topic

[tunt01]

NLRP3 inflammasome is inhibited by several things like intermittent fasting and SIRT3 expression. [1]

 

If Nicotinamide Riboside makes it into the brain, it probably also inhibits NLRP3.  [2]

 

 

 

  1.  Traba, J., Kwarteng-Siaw, M., Okoli, T., Li, J., Huffstutler, R., & Bray, A. et al. (2015). Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. Journal Of Clinical Investigation, 125(12), 4592-4600. doi:10.1172/jci83260

 

 

2.  Nicotinamide Riboside Ameliorates Hepatic Metaflammation by Modulating NLRP3 Inflammasome in a Rodent Model of Type 2 Diabetes | Abstract. (2016). Journal Of Medicinal Food. Retrieved from http://online.lieber...9/jmf.2015.3439

Edited by prophets, 15 August 2016 - 11:16 PM.

[mag1]

In the USA, wholesale price of a week's supply of generic mefenamic acid has been quoted as $426.90 in 2014. Brand-name Ponstel is $571.70.^[16] In contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.^[17] In the Philippines, 10 tablets of 500 mg generic mefenamic acid cost PHP39.00 (or the equivalent of $0.88USD)as of October 25, 2014.

 

wiki

[resveratrol_guy]

In the USA, wholesale price of a week's supply of generic mefenamic acid has been quoted as $426.90 in 2014. Brand-name Ponstel is $571.70.^[16] In contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.^[17] In the Philippines, 10 tablets of 500 mg generic mefenamic acid cost PHP39.00 (or the equivalent of $0.88USD)as of October 25, 2014.

 

wiki

 

What a racket! The cocaine mafia must be envious.

 

It looks to me as though salsalate is safer than mefenamic acid, but in theory both of these could be used together to achieve a synergistic result because, although both are NSAIDs, they work on different targets in the brain and affect different plaque species.

 

The authors note: "Mefenamic acid is used routinely in clinical practice and so we tested the effects of mefenamic acid in an in vivo model of Aβ-induced memory loss". This is kind of unfortunate because flufenamic acid appeared to perform better in vitro.
 

[resveratrol_guy]

They should fast track it. If they can release the Ebola vaccine early why can't they do the same for the AD vaccine?

 

They could clearly do that. In fact, several promising cancer drugs have been fast tracked recently. But if you follow the news stories, it's quite clear that they're only being given to desperate end stage patients. A modest percentage of those patients have gone into remission, which is fantastic. But the cost is still prohibitive, and it seems unlikely that early stage patients would be granted access to them. That may eventually occur, and trials are ongoing, but it's a question of years if not decades.

 

I see no reason to think that the FDA and other glacial regulatory bodies such as the NHS would look at tau vaccine any differently. After all, their collective mission is to collect paychecks and avoid liability, not to help people. This is ironic considering that most of their employees actually do want to help people, but on an institutional level, the incentives are all upside-down.

 

On the plus side, unlike with cancer, I suppose it's possible to fake advanced AD by being grossly unresponsive at the doctor's office. I don't think doing so would be unethical, either, considering that people's lives are at stake here, and every vaccine in history has been more effective prior to the onset of end stage disease. But even for this strategy, you'll need to wait for the approval of tau vaccine. Considering that phase 2 is underway and phase 3 isn't even on the table, you're still looking at close to a decade. If you're interested, my recommendation would be to contact Axon Neurosciences and see if there's any backdoor route to obtaining it, for example, by participating one of their trials.

[resveratrol_guy]

NLRP3 inflammasome is inhibited by several things like intermittent fasting and SIRT3 expression. [1]

 

If Nicotinamide Riboside makes it into the brain, it probably also inhibits NLRP3.  [2]

 

So I've been taking honokiol (a SIRT3 agonist) and NR for the better part of a year now. I can't say they've hurt, and I'm pretty they've helped a bit, but in both cases, the effects are rather muted at this point. I certainly wouldn't look to these compounds for neurological health benefits before investigating cheaper options that might be more effective (hence my recent interest in prescription NSAIDs, for example). It's possible, though, that your strategy would be much more effective against cancer than neurodegeneration.
 

[ceridwen]

Where can Salsalate and flufenamic acid be bought cheaply?

[ceridwen]

Could be that big pharmacy is trying to get rid of drugs they can't use because the side effects are too awful
So they repurpose them.

[ceridwen]

Vaccines historically have a bad reputation also

[tunt01]

 

 

So I've been taking honokiol (a SIRT3 agonist) and NR for the better part of a year now. I can't say they've hurt, and I'm pretty they've helped a bit, but in both cases, the effects are rather muted at this point. I certainly wouldn't look to these compounds for neurological health benefits before investigating cheaper options that might be more effective (hence my recent interest in prescription NSAIDs, for example). It's possible, though, that your strategy would be much more effective against cancer than neurodegeneration.
 

 

 

I take honokiol daily also.  I think it's helpful.  I am probably more sensitive than most to the cardiovascular effects.  IMO, aging is a game of inches.  I think the importance of SIRT3 expression is rather great and associated with many aspects of longevity, while avoiding the negatives of detrimental conditions like metabolic syndrome,   I'll continue to take it, as I'm sure you probably will also, regardless of whether or not I "feel" it.

 

In terms of neurodegeneration vs. cancer, I honestly do not know as much about the cancer aspect to draw a comparison.  Nicotinamide and Nicotinamide Riboside have a fair amount of data showing their importance in preventing neurodegeneration in what is probably a SIRT1 mediated manner (upstream from PGC-1a, BACE1, role in autophagy/proteostasis etc.).

 

There is some data saying NR doesn't really effect the brain [1], but other data seems to suggest it does [2].  I'm not sure what the correct answer is really, but my inkling is the latter is probably more accurate.

 

 

[1]  Carles Cantó, J. (2012). The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity. Cell Metabolism, 15(6), 838. Retrieved from http://www.ncbi.nlm....les/PMC3616313/

 

 

[2]  Bing Gong, G. (2013). Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models.Neurobiology Of Aging, 34(6), 1581. Retrieved from https://www.ncbi.nlm...les/PMC3632303/

 

 

 

 

 

[resveratrol_guy]

The NR mouse study used 250 mg/kg. That would probably alleviate just about anything, LOL! Seriously, what's the HED on that? Unlike with drugs neutralized by the liver, the conversion in this case might require straight up multiplication by weight ratio. In any event, it must be well into the grams per day. Unless it removes all your brain plaque in a month, I don't think it's a viable economic proposition for most of us. And those of us who would try it would be well advised to space out the dosing quite rigorously, so as to avoid the possibility of liver overload, which is still poorly understood for NR as opposed to niacin or niacinamide.

I plan to scale back on honokiol in the future. It's quite expensive to get the properly tested stuff. On the other hand, anyone using insulin or growth hormone other than NGF should probably stay on it in order to forestall cancer, especially brain cancer.

@ceridwen: If you google around, salsalate is pretty easy to find. Try "buy salsalate" or stick a country name on the end. I honestly don't believe that drug companies are trying to repurpose it because it's dangerous. It actually seems less dangerous than aspirin with respect to gastrointestinal bleeding. (Mefenamic acid, however, is a different story.) It should work well if paired with a few months of intranasal insulin.

The most important considerations when taking NSAIDs are: (1) know about Reye's syndrome and how to detect it, (2) take steps to avoid stomach ulcers, and (3) especially with the more powerful ones, avoid situations in which you're likely to experience sudden surprises or high stress, which could lead to strokes that bleed excessively. Although I think all these risks are manageable, they need to be taken seriously by patients on powerful blood thinners; for its part, salsalate is less dangerous in this regard than aspirin, although we're talking about 1350 mg/d of salsalate vs. the typical 81 mg/d prophylactic aspirin. (I remember how my grandmother was startled when lightning struck and exploded a power transformer next to her house, for example. The shock was very brief but raised her blood pressure high enough to destroy her right retina. She went on to live another 27 years, but never regained her vision. I never forgot this, so in the rare case that something startles me so severely, I try to raise my hands and stand up if possible, so as to mitigate the blood pressure shockwave before it reaches my brain; obviously, there are situations such as driving where this is not advisable.)

[tunt01]

The NR mouse study used 250 mg/kg. That would probably alleviate just about anything, LOL! Seriously, what's the HED on that? Unlike with drugs neutralized by the liver, the conversion in this case might require straight up multiplication by weight ratio. In any event, it must be well into the grams per day. Unless it removes all your brain plaque in a month, I don't think it's a viable economic proposition for most of us. And those of us who would try it would be well advised to space out the dosing quite rigorously, so as to avoid the possibility of liver overload, which is still poorly understood for NR as opposed to niacin or niacinamide.

 

The other study had 400 mg/kg NR in a C57Bl/6J mice.  See Fig 5A below which shows low NAD+ content in the brain (suggestive that NR doesn't reach this tissue adequately).  The 250 mg/kg study was Tg2576 mice.  It may be the model difference.  It may be the low NRK expression.  I don't know.

 

Brenner and Guarente seem to both think NRK enzymes are in the brain sufficiently that NR gets into the brain and is metabolized.

 

I'm not sure what the ultimate answer is yet.

 

[docmaas]

hed for mice: mouse dose/12 * wt in kg or @1.4g for 70kg person.  hed for rat: rat dose/6 * wt in kg 

 

Mike

The NR mouse study used 250 mg/kg. That would probably alleviate just about anything, LOL! Seriously, what's the HED on that? Unlike with drugs neutralized by the liver, the conversion in this case might require straight up multiplication by weight ratio. In any event, it must be well into the grams per day. Unless it removes all your brain plaque in a month, I don't think it's a viable economic proposition for most of us. And those of us who would try it would be well advised to space out the dosing quite rigorously, so as to avoid the possibility of liver overload, which is still poorly understood for NR as opposed to niacin or niacinamide.

I plan to scale back on honokiol in the future. It's quite expensive to get the properly tested stuff. On the other hand, anyone using insulin or growth hormone other than NGF should probably stay on it in order to forestall cancer, especially brain cancer.

@ceridwen: If you google around, salsalate is pretty easy to find. Try "buy salsalate" or stick a country name on the end. I honestly don't believe that drug companies are trying to repurpose it because it's dangerous. It actually seems less dangerous than aspirin with respect to gastrointestinal bleeding. (Mefenamic acid, however, is a different story.) It should work well if paired with a few months of intranasal insulin.

The most important considerations when taking NSAIDs are: (1) know about Reye's syndrome and how to detect it, (2) take steps to avoid stomach ulcers, and (3) especially with the more powerful ones, avoid situations in which you're likely to experience sudden surprises or high stress, which could lead to strokes that bleed excessively. Although I think all these risks are manageable, they need to be taken seriously by patients on powerful blood thinners; for its part, salsalate is less dangerous in this regard than aspirin, although we're talking about 1350 mg/d of salsalate vs. the typical 81 mg/d prophylactic aspirin. (I remember how my grandmother was startled when lightning struck and exploded a power transformer next to her house, for example. The shock was very brief but raised her blood pressure high enough to destroy her right retina. She went on to live another 27 years, but never regained her vision. I never forgot this, so in the rare case that something startles me so severely, I try to raise my hands and stand up if possible, so as to mitigate the blood pressure shockwave before it reaches my brain; obviously, there are situations such as driving where this is not advisable.)

 

[resveratrol_guy]

As I said, I really don't think the standard HED formula applies, because NR is essentially a vitamin, not a drug which the liver perceives as toxic and attempts to neutralize. The other problem is that 1 g/d is sort of the upper safe limit for niacin and niacinamide, so it's at least questionable as to whether or not 1.4 g/d of NR would be safe. If anyone wants to try that for a month, be my guest, but watch your liver enzymes.

 

Speaking of which, I read up a bit more on mefenamic acid and salsalate. It seems that they can both cause kidney and liver stress and perhaps thyroid depression. I suppose, as usual, it comes down to one's lifestyle and diet. It's never clear in the side effect reports what else was going on when someone reported an adverse effect. There's also a big difference between reversible suppression and actual damage, which means you need to read the details if you plan to take either of them.

 

By the way, I was able to confirm that mefenamic acid (Ponstel and generics) is available from several dodgy online pharmacies in India and Mexico. Salsalate (sold by 3M as Disalcid) is harder to come by for some reason. It occurred to me that one could buy several brands, then keep only the ones which tasted similar (and maybe bitter like aspirin?), going on the theory that real drugs should always taste the same, but fake ones should have various tastes. Of course proper lab analysis would be the best plan, but unless we do a group buy, that's not going to affordable for most of us.

[Mian Ali Ismail]

CAN THIS BE USED FOR NEURODEGENERATIVE DISEASE IN THE ARTICLE IT SAYS IT COULD ! ! !

Scientists Activate Brain of Patient Coming Out of Coma

 

At the University of California, Los Angeles clinical researchers have successfully used focused ultrasound to “jump-start” the brain of a man coming out of a coma. The 25-year-old patient was barely conscious once he woke up from the coma, but soon after the initiation of treatment his condition improved measurably.

The ultrasound approach was tried as an alternative to deep brain stimulation that actually requires conductive metal leads to reach the thalamus. Deep brain stimulation can be both difficult and dangerous, so any opportunity for alternatives is very exciting.

The team used a device from BrainSonix, a company founded by one of the study authors, that delivers narrowly focused beams of ultrasound in short bursts. It was aimed at the patient’s thalamus and activated ten times for thirty seconds during a ten minute treatment session. Following treatment the patient showed signs of improvement and three days later there was marked improvement in the form of full consciousness and ability to communicate with clinicians by nodding and shaking the head.

These findings are quite promising and following the initial proof-of-concept the next steps will involve verifying the results in more patients.

Study in journal Brain Stimulation: Non-Invasive Ultrasonic Thalamic Stimulation in Disorders of Consciousness after Severe Brain Injur

[ceridwen]

Do old people even have a thalamus?

[mag1]

The truly difficult stage when caring for those with dementia is coping with the progression through moderate dementia.

With moderate dementia, patients still have enough physical energy to become agitated (but without cognitive ability

to properly direct this energy). For our loved one this lasted a few months and has been by far the most difficult part of the

illness process.

 

We thought that perhaps there was a secret way to manage these behaviors, though apparently this is not

true. During this time our loved one was briefly hospitalized and they immediately treated with a range of anti-psychotics

and sleeping pills. Anti-psychotics are known to be dangerous for dementia patients and the FDA imposed a large

fine on pharmaceutical companies that marketed them for off-label use for AD agitation.

 

One thing that occurred to me is that the solifenacin Aricept combo could be a great alternative to the anti-psychotics. 

​Patients could be treated with this combo right until they have reached the agitation stage and then treatment could

be withdrawn. The patients would immediately crash through moderate dementia and would then be too impaired to injury themselves

or others. Treatment could with combo treatment could resume once they had progressed enough not to be in the agitation state. (Perhaps if

these patients were treated with the combo occasionally during this stage then the full agitation behavior might not manifest.) 

 

This might not be the best possible solution, though it would certainly be much better than what dementia patients

currently experience during this stage of their illness.

 

   

Edited by mag1, 27 August 2016 - 02:11 AM.

[Der Springende Punkt]

The truly difficult stage when caring for those with dementia is coping with the progression through moderate dementia.

With moderate dementia, patients still have enough physical energy to become agitated (but without cognitive ability

to properly direct this energy). For our loved one this lasted a few months and has been by far the most difficult part of the

illness process.

 

We thought that perhaps there was a secret way to manage these behaviors, though apparently this is not

true. During this time our loved one was briefly hospitalized and they immediately treated with a range of anti-psychotics

and sleeping pills. Anti-psychotics are known to be dangerous for dementia patients and the FDA imposed a large

fine on pharmaceutical companies that marketed them for off-label use for AD agitation.

 

One thing that occurred to me is that the solifenacin Aricept combo could be a great alternative to the anti-psychotics. 

​Patients could be treated with this combo right until they have reached the agitation stage and then treatment could

be withdrawn. The patients would immediately crash through moderate dementia and would then be too impaired to injury themselves

or others. Treatment could with combo treatment could resume once they had progressed enough not to be in the agitation state. (Perhaps if

these patients were treated with the combo occasionally during this stage then the full agitation behavior might not manifest.) 

 

This might not be the best possible solution, though it would certainly be much better than what dementia patients

currently experience during this stage of their illness.

 

Very good point, mag. This could be even potentiated with 5-HT6 antagonists (e.g. Lundbecks Idalopirdine coming 2017 or 2018).

 

[resveratrol_guy]

 

CAN THIS BE USED FOR NEURODEGENERATIVE DISEASE IN THE ARTICLE IT SAYS IT COULD ! ! !

Scientists Activate Brain of Patient Coming Out of Coma

 

At the University of California, Los Angeles clinical researchers have successfully used focused ultrasound to “jump-start” the brain of a man coming out of a coma. The 25-year-old patient was barely conscious once he woke up from the coma, but soon after the initiation of treatment his condition improved measurably.

The ultrasound approach was tried as an alternative to deep brain stimulation that actually requires conductive metal leads to reach the thalamus. Deep brain stimulation can be both difficult and dangerous, so any opportunity for alternatives is very exciting.

The team used a device from BrainSonix, a company founded by one of the study authors, that delivers narrowly focused beams of ultrasound in short bursts. It was aimed at the patient’s thalamus and activated ten times for thirty seconds during a ten minute treatment session. Following treatment the patient showed signs of improvement and three days later there was marked improvement in the form of full consciousness and ability to communicate with clinicians by nodding and shaking the head.

These findings are quite promising and following the initial proof-of-concept the next steps will involve verifying the results in more patients.

Study in journal Brain Stimulation: Non-Invasive Ultrasonic Thalamic Stimulation in Disorders of Consciousness after Severe Brain Injur

 

 

I suspect that this is a mechanical form of hormesis. If that's true, then the benefits should be similar to those of a mild CT scan, except that in this case, the trauma was delivered to the thalamus in particular, as opposed to the entire brain.

 

Moreover I suspect that generalized brain ultrasound therapy would be synergistic with LLLT, the latter providing the energy to take advantage of the hormetic response to the former. However, as with any hormetic process, the question of dose is critical. We need enough ultrasound to activate a healing response, but not enough to cause widespread capillary damage. I have no idea where that threshold lies, although some animal experiments have been conducted.

 

Mainly, I think this would serve as dementia prevention, and not so much as treatment. Remember that the patient in this case, although technically demented, was actually suffering from a concussive injury and was otherwise neurologically normal.
 

[mag1]

Another good one maybe to combine with CPC201 might be Axona.

The whole idea would be to get everything working to top performance just until the agitation set in and then crash through it.

 

The current medications do not even give you enough symptomatic benefit for this strategy to work. However, what the research

is saying about CPC201 is that nearly everyone has a fairly large response, though it is not disease modifiying.

 

This could be great for the workers in dementia care trying to cope with an entire ward of moderate AD patients. I really do not

see how they could possibly manage without pulling out bottles of anti-psychotics and dosing everyone (probably the workers

would even need a dose here and there). The maximize and crash strategy could be a way around all of that.     

[mag1]

Am I the only one slightly frustrated with the LMTX story?

taurx is claiming that the second phase 3 trail in AD with LMTX is a lock to report a positive result for the modified primary analysis.

 

They have known about this result for almost a year now.

The numbers would have shown that those in the phase 3 trials taking standard of care would not benefit fron adding on LMTX years ago.

Who knows how much longer this will drag on before an add on mini phase 3 trial is annoucned.

 

If taurx believes their result is valid, then why don't they step up and get this conclusive study in motion?

Perhaps 100 monotherapy patients treated with LMTX and a placebo arm could tell us with reasonable certainty

whether or not this is a valid result within a year. The trial would not even have to reach significance itself, it could be added

together with the other results in a meta analysis.

 

Dementia is already a global crisis.

Why doesn't taurx move this ahead?

(They might also think of starting a compassionate use program. Considering the size of the reported benefit,

it would likely not take very long to verify their phase 3 claims.)    

  

[mag1]

LMTX phase 3 number 2 should be reported Thursday or Friday (Munich time).

Very exciting!

 

If they could report an unambiguous positive primary readout for the bvFTD trial, then

the entire interpretation for LMTX in AD could shift.

 

http://taurx.com/tau...-dementia.pdf  

[tunt01]

Paper:  http://dx.doi.org/10.1038/nature19323

 

Pretty big news.  Aducanumab clears nearly all amyloid in patients brains over 54 weeks in a dosage dependent manner from testing levels of 3 mg/kg and 10 mg/kg.  MMSE testing was improved vs. controls in all subjects taking the medication.

 

 

I've been rather skeptical of ABeta immuno therapies.  But the interesting part about Aducanumab is that it seems to only target fibrils and plaques, while leaving monomer Abeta alone.  That's fairly interesting.  I've no idea what the side effects are, but the drug is certainly something to watch.

 

 

 

Edited by prophets, 01 September 2016 - 05:03 PM.

[mag1]

Anyone heard of the results for the taurx phase 3 in FTD?

They should be out by now. 

 

"will now be reported for the first time at the 10th International Conference on Frontotemporal Dementias (ICFTD) in Munich on 31 August-2 September 2016." 
 

[resveratrol_guy]

Paper:  http://dx.doi.org/10.1038/nature19323

 

Pretty big news.  Aducanumab clears nearly all amyloid in patients brains over 54 weeks in a dosage dependent manner from testing levels of 3 mg/kg and 10 mg/kg.  MMSE testing was improved vs. controls in all subjects taking the medication.

 

 

I've been rather skeptical of ABeta immuno therapies.  But the interesting part about Aducanumab is that it seems to only target fibrils and plaques, while leaving monomer Abeta alone.  That's fairly interesting.  I've no idea what the side effects are, but the drug is certainly something to watch.

 

It still did not stop decline. But perhaps in combination with other therapies, it would, especially in the early stages of disease, if not the preclinical state.

 

There are enough people affected by AD that it's possible to imagine a future in which this treatment is economical. What's virtually impossible to imagine, however, is an FDA willing to allowing patients to take it when they most need it, which is in middle age before symptoms manifest. Let alone an insurance industry willing to fund that, considering its increasing focus on treating symptoms instead of disease.

 

Just the same, this study proves that monoclonal antibody therapies are a viable, if incomplete, strategy against AD.

 

The other major AD immunotherapy under study, tau vaccine, consists of fragments of misfolded tau, as opposed to antibodies which bind it. But presumably the same chain of events could ensue, leading the microglia to attack misfolded tau in the brain, but only after a few months during which antibodies would form naturally.

 

The best immunotherapy for AD would involve: (1) targetting all major forms of brain plaque, (2) delivering antibodies to bind with plaque, tagging it for prompt removal by the microglia, (3) broad immune exposure to the misfolded proteins, and perhaps (4) direct engineering of microglia to recognize it, after the fashion of exogenous macrophage modification for cancer or HIV treatment., followed by reinjection. Ideally, stem cell lines would be CRISPRed to disable AD genes as well. (This is under current research, although from what I've read the current problem is that CRISPR/Cas9 is too big to cram through the tight junctions in the BBB, so one startup is trying to discard redundant nucleotides in the system to save space. Another approach would be craniotomy, but this only has an effect radius of a centimeter or so, if Liz Parrish is correct.)

 

But I digress. Of all these points, the most economical solution would probably be tau vaccine. It doesn't act immediately, but on the other hand it would not need to be given chronically forever, as presumably aducanumab would. I can actually foresee a future in which a loosely regulated banana republic makes tau vaccine available for sale to anyone who wants it, not unlike flu vaccine.

 

The significance of this trial, in my view, has little to do with the amyloid hypothesis, which is at best insufficient to produce the cure to AD. Rather, it comes down to the notion that, as we suspected, immunotherapy is promising to be as effective in AD as it is in cancer. The central question now is when any sufficiently potent form of immunotherapy is likely to be available for a reasonable cost.

 

The best answer to that question, if you can wait 8 years or so, is probably tau vaccine. Meanwhile, eat like a monk.

Edited by resveratrol_guy, 02 September 2016 - 10:45 PM.

[mag1]

What I have been quite impressed with in these aducanumab results is that there seems to be a reasonably good chance of actually treating

a broad disease classification such as Alzheimer's with a single compound. The only genetic stratification that they are talking about is

APOE epsilon 4 positive and negative.

 

This is quite remarkable. With cancer, researchers seem to now be resigned to treating narrowly

defined sub sub types which usually results in limited market potential for their products and thus very high costs to the patient.

 

Drugs that could effectively treat a large portion of clinical Alzheimer patients would have a global market of tens of millions of patients.

[Some of the recent breakthrough cancer drugs had a potential US market of perhaps 10,000 or less patients.]  

 

I wonder when the Alzheimer political power base will step forward and ask to accelerate the aducanumab phase 3s?

We are already one year into the two phase 3 set to enrol 2700 patients. Do we really want to let these trials run their course until

2020 or 2022? I would think that there are quite a few tens of millions in the Alzheimer community who might not want to wait it out for the next

few years. Why not do an interim  analysis in a year? If the results were shown to be moving in the right direction, why not step up with

a billion dollar tax credit for Biogen to add another 1000 patients perhaps with APOE epsilon 4 (say 75% in the treatment arm) to accelerate

the trial? Here again this is not charity. Alzheimer's already costs the global economy well over $1 billion PER DAY. A would think that

investing a billion in such a way would repay itself many many times over. Biogen, though left to its own devices, would not be motivated to spend a billion to

hurry the transit of its antibody through the pipeline.   

 

 

Perhaps the surprise with the approaching Alzheimer's treatments might be how low the prices are.

The most effective medical treatments ever invented, vaccines, while being extensively researched and highly effective are quite modestly priced.

When everyone buys a medicine the research costs are spread over the entire population. Biogen was talking about the trials for aducanumab costing

$2 billion. Everyone up to tossing in $5-$10 to cover these costs? Everyone does develop Alzheimer pathology eventually, so this is not charity.

 

For most diseases, especially cancer, when they pass the hat around, people are expected to pony up a few hundred thousand because the patient

populations affected are often small. 

 

 

I will be very very interested in seeing how Biogen prices its antibody if it were to be shown to be effective.

These companies are in the business of profit maximization. It should be remembered that even for a monopoly profit maximization is not

equal to price maximization. There would simply be a truly massive market for lifestyle anti-amyloid treatments. However, if Biogen were to

unwisely try to go the price maximization route, then it would lose a simply huge amount of its potential revenue.

 

The recreational anti-amyloid market (where the large revenue potential would be) would probably be willing to pay up to $2000 per year.

If Biogen chose a price point closer to $50,000, then it would lose the entire recreational market. They could simply wait for the patent to expire.

 

{Anyone know when the aducanumab patent expires?} 

 

Wonder if Biogen could think up a way to have a dual price marketing strategy. Price the product at $50,000 for those with clinical AD and $2,000 for

those who would much prefer never knowing what clinical AD was all about.

 

The great example here was anti-cholesterol drugs. These lifestyle drugs were the most successful products to ever reach the market. The pharmas did not make the

mistake of trying to price maximize.

   

Edited by mag1, 03 September 2016 - 12:09 AM.

[resveratrol_guy]

Look if we can't even get drugs to people economically in order to prevent bee sting allergies (EpiPen), how on Earth do you think we'll faciltate recreational amyloid reduction? This isn't about morality, or science, or even profit. It's about bureaucracy. The FDA, NHS, and similar institutions are like giant asses continually farting on the industry. They shut down research like 23andMe, converting a brilliant genomic information resource into a useless infomational website about finding your 5th cousins. They impede basic sanitation, just today banning Triclosan, the antibacterial agent used to guard against deadly infections for decades because we "don't know enough" about its safety. Truth-in-advertising should be their enforcement charter, and nothing more. There is absolutely no way that they would ever allow what you're talking about with respect to prevention. If nothing else, imagine the cost of patented aducanumab injections every month for life starting at 50 or 60, to say nothing of all the lawsuits that would rage on for years because someone died while on the drug, so therefore the drug is to blame.

Sorry to be so jaded, but I've watched this circus for decades. It's been accurately described as "Moore's Law in reverse". We need countries like China, India, Mexico, and Thailand to step up the pace. People are dying. This is serious. We are depending on bureaucrats for our lives, which is a pathetic totalitarian irony in the otherwise democratic West.

Don't write to your Congress person. Nothing will change because the system is so knotted up on itself. The only reasonable strategy is to invest aggressively while you're healthy so you can buy a plane ticket to a gene therapy center when it becomes available. The best thing you can do for yourself is develop extreme risk tolerance and a deep awareness of the scientific data that can help you, like Elon Musk. Trust me, you're going to need the money.
 

Edited by resveratrol_guy, 03 September 2016 - 03:23 AM.

[resveratrol_guy]

Here is a new strategy for dementia prevention which costs virtually nothing and might make a significant impact. It's not controlled by the FDA, and it could complement all the other good advice we've received on Longecity.

[mag1]

LMTX phase 3 in bvFTD did not achieve its co-primary endpoints.

 

http://taurx.com/trx...rial-update.pdf

Edited by mag1, 04 September 2016 - 03:36 PM.

[tunt01]

 

It still did not stop decline. But perhaps in combination with other therapies, it would, especially in the early stages of disease, if not the preclinical state.

 

 

 

I don't have the study in front of me, but when I looked at it, the treatment group MMSE was materially and dramatically better than the controls.  Yes, treatment declined slightly, but it was nothing compared to controls.

 

You don't find that compelling?  Just the fact that amyloid is cleared in such a dramatic fashion, which likely has a downstream effect on Tau and ultimately improved MMSE scores, seems extremely compelling to me.

 

I personally wish there was a better answer for removal of Abeta than a monoclonal antibody.  But this drug seems like it could be some kind of legitimate answer, in the absence of any better alternative really.

[mag1]

I like aducanumab too. It was discovered by sampling antibodies from seniors who did not develop AD. In a sense it has already been shown to be safe and effective because it was derived from these non-AD individuals. Of course, the question of dosing up to try and eliminate the large burden of amyloid within 1 year for those with clinical symptoms changes the possible safety and efficacy of this antibody. I would think that there would be a fairly large market of worried well who would be quite happy to take occasional low doses of this antibody as a preventative.

 

alzforum has made a point of trying not to read too much into the cognitive changes.

The third comment noted that there was a large difference in the drop outs in the 10 mg/kg dosing arm that might explain

the apparent benefit for these patients.

http://www.alzforum....tudy-published 

 

It should also be remembered that with the 1792 vaccine some of the patients had all of their amyloid cleared from their brains and yet still continued to progress to severe dementia.