The authors report that restoring NAD+ balance in the brain -- using a compound called P7C3-A20 -- completely reversed Alzheimer's pathology and recovered cognitive function in two different transgenic mouse models (one amyloid-based, one tau-based). The mice had advanced disease before treatment began.
- There's room for skepticism. As Derek Lowe once wrote: "Alzheimer's therapies have, for the most part, been a cliff over which people push bales of money. There are plenty of good reasons for this: we don't really know what the cause of Alzheimer's is, when you get down to it, and we're the only animal that we know of that gets it. Mouse models of the disease would be extremely useful – you wouldn't even have to know what the problem was to do some sort of phenotypic screen – but the transgenic mice used for these experiments clearly don't recapitulate the human disease. The hope for the last 25 years or so has been that they'd be close enough to get somewhere, but look where we are."
- If the drug's mechanism of action has been correctly assigned, it's very plausible that simply supplementing with NMN, NR, or NADH would work equally well. The authors caution against this on, IMO, extremely shaky and unjustified grounds. "Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer."
There are numerous chemical supply companies that will list chemicals like this “for sale”. They might not have it in stock but they hope they’ll get your search traffic and be able to synthesize it if you place an order.
If you look at the amounts, they’re tiny. I don’t know the doses that would be used in humans but typically ordering from chemical supply shops would be economically infeasible for just about any drug. These are meant for one-off studies and experiments, not ongoing human use.
There have been a growing number of online groups arranging to do group buys of synthesized experimental drugs based on studies. I’ve followed a few of them and the results range from people losing their money, receiving product that is too contaminated to use, or in some cases they go to great lengths to verify the chemical but then discover it doesn’t do what the original study promised it would do. In some of the more horrifying cases I’ve seen forum posts from people reporting long lasting chest pains from one chemical, and another chemical was sending people into psychosis. So if (when) these chemicals start appearing on group buy sites I suggest ignoring it until more research is done. Making yourself into a lab rat is not a good idea.
And there's room for thinking there's water in the ocean. We have no idea whether this would work at all or how it would work at all in humans. We have one experiment in mice, which as you say can't have Alzheimer's.
This is a nice step, like developments in fusion energy. That's part of research, and let's hope and investigate it, but it's absurd to think about it as anything but a science project right now.
Sadly, it's worse. We don't have one experiment that works in mice: we have dozens, if not hundreds. We've cured "Alzheimer's in mice" many times over. The treatments never work in humans, because it's not the same disease. We don't know the root cause of the human disease and so we can't model it accurately in mice.
I totally get that people are not mice, however animals studies have been useful for all sorts of diseases. Are they really uniquely bad for Alzheimer's?
And the author of the paper has disclosed that they have patent on the drug being tested. Let's see if the results can be reproduced by others. Then let's see how it tests with humans.
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer.
As someone who's seen both cancer and Alzheimer's up close, that would be a very easy choice.
Except that time of death comes on average many years later for Alzheimer's than cancer. In the same thought, better die from heart attack instantly but unfortunately much earlier, which would be devastating for the relatives.
From multiple personal experiences, including both of my parents, dementia is a slow, horrible death where you are robbed of your dignity and end up dragging all of your relatives through a very long, very torturous hell. You will be drooling, pissing, and shitting yourself, all while slowly reverting back to a low IQ childhood mentality where you're very likely to have outbursts and verbally or physically attack the people around you. Your loved ones will be tormented, and if you don't have loved ones then if you're lucky you'll be tossed into a room and forgotten about by underpaid, overworked staff at some run-down nursing home. If you're not lucky you'll be laying in a gutter on the street until you die.
Interestingly my wife helped a friend whose father had the disease during the pandemic.
He had worked as a professor and after retirement had suffered with AD for years but had stayed "independent" because his wife was high functioning mentally but low functioning physically and formed a good team.
He'd bought long term care insurance so he had the resources to afford both a room at a care home but also personal help from home aides, including my wife. He didn't really know what was going on most of the time but he never got angry or flustered and was always pleasant to deal with.
We had trouble with certain homes having a way they want to do things or requiring things that weren't really necessary, one insisted that he get a pacemaker because he had bradycardia. When he lived with his son between homes probably the most difficult thing was that he got up in the night to use the bathroom and would end up urinating in the wrong place. He got much better care than many residents because people were always coming around to see him and the staff knew that we cared and would advocate for him.
He passed away at 92 and outlived many of the people who knew him at work so he had just a small memorial ceremony. I saw it as an example of healthy aging and talked about it a lot with my wife -- and it made me think about myself and my own fear that my ability to compensate for my schizotaxia may degrade when my brain degrades and I can picture myself becoming really nasty and it gives me all the more incentive to rewrite my habits while I still can.
Sadly, cancer isn’t one singular disease. Types of cancer can be excruciatingly painful for many years, which is also tormenting to everyone around you. I wouldn’t wish either on anyone.
Cancer. The worst types of it have the advantage of killing quickly. Alzheimer's destroys the self, and you survive a long time with it, leading to much more suffering, both to you (to the extent you continue to exist) and to your family.
I have a different perspective. The worst types of cancer kill slowly and cause agonizing suffering.
Alzheimer's leads to negative outcomes for your caregivers, but by many accounts many affected individuals do not suffer all that much, if at all, due to their lack of awareness.
If I were diagnosed with Alzheimer's, I would seek out assisted suicide. But I think it's more complicated than that: its existence incentivizes pushing people toward assisted suicide. The government finds a way to help with bloated medical care budgets; unscrupulous family members guilt trip the sick to choose the option to keep the inheritance intact.
The best solution allows it for severe cases, while still investing money in research and spending money for palliative care so it remains an option and not a demand. But that's a tricky line to maintain.
My grandmother's case ended up bankrupting my grandfather and seriously straining the rest of the family. Which ultimately put my grandfather in a pennyless position when he was in his 90's, and poor state care when he was declining - not what he or my grandmother worked their entire lives for. Our family couldn't replace what was lost in the years of care for my grandmother's body, long after she herself was gone.
Never something she would have wanted, but you don't really have a choice and dignified death is never given as an option.
Is this the same NAD+ that’s prescribed by longevity / hormone clinics?
Edit: after some googling, sounds like NAD+ (which you can get from real doctors) is the “building blocks” similar to how protein is the building blocks for muscle, while the experimental compound changes/enhances how the building blocks are used inside your cells.
So you might need some NAD+ precursor like NMN and this compound for it to work in humans because by the time you’re old it’s much harder for your body to make. Was the experiment done in older mice or younger ones that have NAD+ but artificial Alzheimer’s ?
Alzheimer's is, by definition, dementia with associated amyloid plaques in the brain. Since you can't detect the plaques without cutting into the brain, the diagnosis is normally given based on symptoms of dementia (significant loss of memory or other cognitive functions) without other clear reasons (no evidence of vascular events, head trauma, brain tumors or other neurological diseases etc).
My understanding is that amyloid plaques can actually be seen with a specialized PET scan now, so it can be more definitively diagnosed in living people.
You mentioned amyloid plaques. What about tau tangles? I thought Alzheimer's required both. If someone (or some dog, for that matter) has amyloid plaques but no tau tangles, is that Alzheimer's? If they have tau tangles but no amyloid plaques, what is it?
And what about the brains that show amyloid plaques, tau tangles, and Lewy bodies? Or plaques plus vascular lesions? At autopsy, most elderly brains show mixed pathology. Does that person have Alzheimer's plus Lewy body dementia plus vascular dementia? Three diseases? Or one brain failing in multiple correlated ways that we've artificially carved into separate categories?
It sounds like we have at least five different pathological markers that correlate with cognitive decline, often co-occurring, with inconsistent symptom mapping. What makes 'Alzheimer's' a disease rather than a region we've named in a high-dimensional space we don't really understand all that well?
> What makes 'Alzheimer's' a disease rather than a region we've named in a high-dimensional space we don't really understand all that well?
Nothing. I think it's sometimes in fact called a syndrome, not a disease per se. Since we don't really understand the mechanism of action, it remains more of a diagnosis by exclusion rather than anything else.
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer.
Does this mean that people are having to trade Alzheimer in exchange for high risk of cancer? Or does this mean that we need better precursors that don't require that trade off?
There's no good evidence that supplementation with NMN, NR, etc. increases the risk of cancer in healthy people. There's some speculation that it might be risky for people with cancer to take those supplements, but the picture is far from clear. Some papers even suggest that they can be beneficial. (e.g., https://pmc.ncbi.nlm.nih.gov/articles/PMC10177531/ )
In terms of risk-benefit analysis, if this stuff actually cures Alzheimer's, then even a 10x increased risk of cancer (all types) is acceptable, as Alzheimer's is frequently a fate worse than death whereas cancer can be managed whilst keeping your personality and sanity intact. In reality, the increased risk of cancer from something like NMN is perhaps 1.005x. To all appearances, totally negligible.
The problem, for Pieper, is that NMN/NR/NADH are ubiquitous and cost pennies per dose. So, if they work (big if), this new research is unmonetizable. The team leads would win a Nobel Prize, but Big Pharma gigabucks are out of the question. Let's see what happens.
Could explain how a compound that's already on the market and has been patented for (some) medical use at least once in 2015 (expiring 2035) might make a good case for "Big Pharma gigabucks"? I thought one reason for a lack of research into "repurposablity" of existing small molecule drugs is the fact that new applications cannot be independently patented?
You absolutely can patent existing drugs. There's a whole scummy pharma industry that takes existing drugs that are widely used off-label and patents that off-label use.
I think it’s worth addressing this with more nuance.
Companies can get a METHOD-OF-USE PATENT (MOU) on an old drug for a new INDICATION.
This gives them the exclusive right to LABEL AND MARKET that drug for that indication for a period of time.
I however, doctors can prescribe and pharmacists can substitute generics for the new indication, regardless of the MOU.
For a company to profit off an MOU, they strategically need to create a new FORMULATION. This is a new dose or delivery mechanism (extended release, topical, etc). A new formulation can be protected with conventional patents that go beyond an MOU.
With an MOU + patent on a new formulation, the company has a brand where they are the only ones allowed to make the new formulation and the only ones with a product approved to be marketed for the new indication.
Getting FDA approval for the new brand is not the main hurdle for the company. To get insurers to pay the premium they want over the cost of existing treatment options, they have to show it’s safer or more effective than those existing options. Otherwise insurance will block it.
In principle, this means that repurposing should only enable companies to profitably repurpose off patent off label applications if they can provide a real patient benefit.
Whether this is the best or most efficient way to promote this kind of innovation, or whether it works as well in practice as it would seem in theory, is a separate question.
Furthermore, we don't even know whether NAD precursor supplementation works. They raise intracellular NAD+ levels, but unclear whether they raise intercellular NAD+, which is what really matters. There are also those that say NAD+ recycling matters more than we think, and precursors don't address that.
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels.
I think it means one should read the very next sentence:
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels.
There’s a lot of umbrella diagnoses that would benefit from more specific diagnostics first. What we call Alzheimer’s is probably actually caused by number of different causes depending on the person. This is true of a lot of things in medicine that get grouped together. That’s why testing a drug in mouse models with all the same characteristics sometimes works but fails to translate into humans who have more variety amongst each other.
The same is true of many diagnoses like pneumonia, cancer, alopecia, essential tremor: there’s multiple different groups that would benefit from different things, and if we had better ways to identify the groups, we’d give them what works for them instead of wasting their time with the wrong treatment. As an example, antibiotics won’t work for viral pneumonia and in addition to wasting the patient’s time, actually harm your microbiome. If you had a perfect way to know which is which, you’d always get the right treatment.
Many disease labels just mean inflammation-of-a tissue / organ.
Worth noting that some viral inflections of the respiratory tract will have a bacterial secondary, where an either commensal bacteria has over proliferated or a pathogenic bacteria has started to get a hold, and treating the bacterial secondary can help the patient better fight the viral primary.
I recall a University of Washington (I think it was) where they were saying they had found Schizophrenia to be a bucket diagnosis, and had discovered that multiple sets of genes were working together in specific testable ways such that there were >4 sub types of Schizophrenia each with its own set of symptoms, and ability to respond to different medications.
The researcher did a follow-up study to confirm their thesis, but I've never seen anyone else follow up on those studies (family with Schizophrenia makes me acutely aware of developments in that field)
A key challenge with Alzheimer’s is there is no good mouse model for the disease. While some approximate the phenotype, it’s not clear that the disease model as commonly studied in mice matches well with mechanisms of the human disease. There’s some thinking in the field that this could be a key reason why so many treatments have appeared very promising in mice and haven’t panned out in humans.
When enough words, framing, and unstated important premises are omitted, it crosses over from the realm of incomplete or misleading into plain outright lying in my worldview.
They claim "Reverses advanced AD in mice." What they did is reverse symptoms in genetic models.
They claim to "Restore NAD+ homeostasis," ignoring that NAD might not even be causally related to Alzheimer’s, just a side effect. It’s like saying we cured a house fire because we efficiently removed the ashes after the fire. It’s the Tau thing all over again.
The claim: "Conservative molecular signatures" when in reality, 5xFAD mice are poor predictors of human clinical success to such a degree that it’s statistically more common for mice studies to NOT transfer to human biology than to do so.
They also make unsupported claims like "Safer than NAD+ precursors (supplements)," when this is a pre-clinical assumption. No human toxicity trials are mentioned in this context, and there are always MASSIVE differences when switching to real human studies. It might be correct, but there’s no basis to say that based on this study.
Also, the senior author owns the company. The paper has the hallmarks of a "pitch deck" for the drug.
In short, it seems to me that the claim of "Full Neurological Recovery" is misleading to patients. It fails to prove that fixing NAD+ in humans will stop the disease, only that it works in mice engineered to have the disease, and only by assuming that their specific measure is a 1-to-1 with the clinical presentation of the disease. The results are likely the "best case scenario" presented to support the commercialization of P7C3-A20.
Here is the COMMON SENSE question peer-reviews should have asked.
Is low NAD+ the fire, or just the ashes?
Why should we believe this works in humans when the last 500 'cures' in 5xFAD mice failed?
Are you regrowing a brain, or just cleaning up a dirty one?
How does one molecule fix five unconnected problems simultaneously? The Context: The drug fixed inflammation, blood-brain barrier, amyloid/tau (protein folding), and memory (neuronal signaling). Drugs rarely hit four distinct biological systems with 100% success....
Where is the toxicology report that proves 'safer than supplements'?
Please... people, do not get your hopes up over this one PR pump piece released on Christmas Day. This is not a legit study. (It might, perhaps, somehow, still be correct, perhaps... even broken clocks are right twice a day... but it's still not a legit study.)
Not my field, but I think a big point here is this isn't purely researching into Amyloid plaques. It is way past time to explore many other possibilities and it is promising to see research in a different direction. This isn't to say Amyloid plaques aren't worthy of research, but when you slam into a wall for a few decades then maybe you should look in different directions now and again.
They mean the fake Alzheimer's they induce by injecting poison into 3 month old animals or which develops in mice genetically engineered to have diseases that aren't Alzheimer's but are somewhat similar to Alzheimer's in some ways, not the kind where you wait 70 years for a human to develop which they don't even really understand what causes it.
I used to work with a guy who had been a scientist at a large pharma company (we were both working at a small biotech start-up at the time).
He told me an interesting story... basically, scientists at his company would get an extra year-end bonus if they had worked on a drug candidate that made it past animal studies and into human (clinical) trials.
He told me that one way to 'consistently' get the extra bonus was to work on candidate drugs for neurological diseases (e.g., Alzheimer's, etc.) because ... the animal models for those diseases were (generally) dog shit, so it was easy to find a drug that 'cured' whatever happened to be your neurological disease of interest in mice/rats/etc.
Then you get your bonus and the drug fails in humans.
Yet another "in mice" breakthrough. The cerebral cortex of a mouse has around 8–14 million neurons while in those humans there are more than 10–15 billion. So scale this outcome by literally 1000x more neurons and wake me when the chimps are remembering how to hold a long conversation.
I don’t get this take. Like yes, we aren’t mice, and everything that works in mice won’t work in humans. But loads of things that worked in mice did wind up working in humans, which is why most groundbreaking drugs over the past decades were first explored in mice, which is why we continue to use mouse models.
Anytime I see headlines like these, I think of the countless animals tortured to death. The sheer level of suffering, all for this Frankenstein nonsense. 90–95% of drugs that appear safe and effective in animal tests ultimately fail in human trials. They mention mice, but there are likely other animals involved, like dogs. Animals deliberately bred with crippling diseases, all for fame and fortune.
More than 110 million animals are killed in the United States each year in experiments. I'd rather just accept Alzheimer's than be complicit in this evil.
I understand the compassion for animals, of course, but not this sentence. Advancing science is not "all for fame or fortune". If it cures people, I can see it. I too would love a world without animal suffering, but I'd also love to not be literally seeing (and I just came back from my parents') my dad slip more and more into nothingness at the hand of this stupid disease.
Three comments:
- You can actually buy the drug here: https://focusbiomolecules.com/p7c3-a20-nampt-activator-prone... It's a simple small molecule. If this stuff works, expect it to be everywhere within just a couple of years.
- There's room for skepticism. As Derek Lowe once wrote: "Alzheimer's therapies have, for the most part, been a cliff over which people push bales of money. There are plenty of good reasons for this: we don't really know what the cause of Alzheimer's is, when you get down to it, and we're the only animal that we know of that gets it. Mouse models of the disease would be extremely useful – you wouldn't even have to know what the problem was to do some sort of phenotypic screen – but the transgenic mice used for these experiments clearly don't recapitulate the human disease. The hope for the last 25 years or so has been that they'd be close enough to get somewhere, but look where we are."
> https://www.science.org/content/blog-post/just-how-worthless...
- If the drug's mechanism of action has been correctly assigned, it's very plausible that simply supplementing with NMN, NR, or NADH would work equally well. The authors caution against this on, IMO, extremely shaky and unjustified grounds. "Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer."
There are numerous chemical supply companies that will list chemicals like this “for sale”. They might not have it in stock but they hope they’ll get your search traffic and be able to synthesize it if you place an order.
If you look at the amounts, they’re tiny. I don’t know the doses that would be used in humans but typically ordering from chemical supply shops would be economically infeasible for just about any drug. These are meant for one-off studies and experiments, not ongoing human use.
There have been a growing number of online groups arranging to do group buys of synthesized experimental drugs based on studies. I’ve followed a few of them and the results range from people losing their money, receiving product that is too contaminated to use, or in some cases they go to great lengths to verify the chemical but then discover it doesn’t do what the original study promised it would do. In some of the more horrifying cases I’ve seen forum posts from people reporting long lasting chest pains from one chemical, and another chemical was sending people into psychosis. So if (when) these chemicals start appearing on group buy sites I suggest ignoring it until more research is done. Making yourself into a lab rat is not a good idea.
And there's room for thinking there's water in the ocean. We have no idea whether this would work at all or how it would work at all in humans. We have one experiment in mice, which as you say can't have Alzheimer's.
This is a nice step, like developments in fusion energy. That's part of research, and let's hope and investigate it, but it's absurd to think about it as anything but a science project right now.
As someone who's seen both cancer and Alzheimer's up close, that would be a very easy choice.
Is this a problem with the molecule or the dose?
He had worked as a professor and after retirement had suffered with AD for years but had stayed "independent" because his wife was high functioning mentally but low functioning physically and formed a good team.
He'd bought long term care insurance so he had the resources to afford both a room at a care home but also personal help from home aides, including my wife. He didn't really know what was going on most of the time but he never got angry or flustered and was always pleasant to deal with.
We had trouble with certain homes having a way they want to do things or requiring things that weren't really necessary, one insisted that he get a pacemaker because he had bradycardia. When he lived with his son between homes probably the most difficult thing was that he got up in the night to use the bathroom and would end up urinating in the wrong place. He got much better care than many residents because people were always coming around to see him and the staff knew that we cared and would advocate for him.
He passed away at 92 and outlived many of the people who knew him at work so he had just a small memorial ceremony. I saw it as an example of healthy aging and talked about it a lot with my wife -- and it made me think about myself and my own fear that my ability to compensate for my schizotaxia may degrade when my brain degrades and I can picture myself becoming really nasty and it gives me all the more incentive to rewrite my habits while I still can.
Alzheimer's leads to negative outcomes for your caregivers, but by many accounts many affected individuals do not suffer all that much, if at all, due to their lack of awareness.
People with the emotional and compassionate depth of a child are the ones keeping us from allowing people to die with dignity.
The best solution allows it for severe cases, while still investing money in research and spending money for palliative care so it remains an option and not a demand. But that's a tricky line to maintain.
Never something she would have wanted, but you don't really have a choice and dignified death is never given as an option.
That's not a universal law, in fact it is different in other countries, i.e. it is something that can be changed.
there are studies about this compound from a decade ago, kinda doubt it's going to be a breakthrough at this point
Edit: after some googling, sounds like NAD+ (which you can get from real doctors) is the “building blocks” similar to how protein is the building blocks for muscle, while the experimental compound changes/enhances how the building blocks are used inside your cells.
Is this actually true? I thought it was pretty common for elderly pets
And what about the brains that show amyloid plaques, tau tangles, and Lewy bodies? Or plaques plus vascular lesions? At autopsy, most elderly brains show mixed pathology. Does that person have Alzheimer's plus Lewy body dementia plus vascular dementia? Three diseases? Or one brain failing in multiple correlated ways that we've artificially carved into separate categories?
It sounds like we have at least five different pathological markers that correlate with cognitive decline, often co-occurring, with inconsistent symptom mapping. What makes 'Alzheimer's' a disease rather than a region we've named in a high-dimensional space we don't really understand all that well?
Nothing. I think it's sometimes in fact called a syndrome, not a disease per se. Since we don't really understand the mechanism of action, it remains more of a diagnosis by exclusion rather than anything else.
Does this mean that people are having to trade Alzheimer in exchange for high risk of cancer? Or does this mean that we need better precursors that don't require that trade off?
In terms of risk-benefit analysis, if this stuff actually cures Alzheimer's, then even a 10x increased risk of cancer (all types) is acceptable, as Alzheimer's is frequently a fate worse than death whereas cancer can be managed whilst keeping your personality and sanity intact. In reality, the increased risk of cancer from something like NMN is perhaps 1.005x. To all appearances, totally negligible.
The problem, for Pieper, is that NMN/NR/NADH are ubiquitous and cost pennies per dose. So, if they work (big if), this new research is unmonetizable. The team leads would win a Nobel Prize, but Big Pharma gigabucks are out of the question. Let's see what happens.
Companies can get a METHOD-OF-USE PATENT (MOU) on an old drug for a new INDICATION.
This gives them the exclusive right to LABEL AND MARKET that drug for that indication for a period of time.
I however, doctors can prescribe and pharmacists can substitute generics for the new indication, regardless of the MOU.
For a company to profit off an MOU, they strategically need to create a new FORMULATION. This is a new dose or delivery mechanism (extended release, topical, etc). A new formulation can be protected with conventional patents that go beyond an MOU.
With an MOU + patent on a new formulation, the company has a brand where they are the only ones allowed to make the new formulation and the only ones with a product approved to be marketed for the new indication.
Getting FDA approval for the new brand is not the main hurdle for the company. To get insurers to pay the premium they want over the cost of existing treatment options, they have to show it’s safer or more effective than those existing options. Otherwise insurance will block it.
In principle, this means that repurposing should only enable companies to profitably repurpose off patent off label applications if they can provide a real patient benefit.
Whether this is the best or most efficient way to promote this kind of innovation, or whether it works as well in practice as it would seem in theory, is a separate question.
Why?
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels.
> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promote cancer. The pharmacological approach in this study, however, uses a pharmacologic agent (P7C3-A20) that enables cells to maintain their proper balance of NAD+ under conditions of otherwise overwhelming stress, without elevating NAD+ to supraphysiologic levels.
The same is true of many diagnoses like pneumonia, cancer, alopecia, essential tremor: there’s multiple different groups that would benefit from different things, and if we had better ways to identify the groups, we’d give them what works for them instead of wasting their time with the wrong treatment. As an example, antibiotics won’t work for viral pneumonia and in addition to wasting the patient’s time, actually harm your microbiome. If you had a perfect way to know which is which, you’d always get the right treatment.
Precision medicine takes this even further.
Many disease labels just mean inflammation-of-a tissue / organ.
Worth noting that some viral inflections of the respiratory tract will have a bacterial secondary, where an either commensal bacteria has over proliferated or a pathogenic bacteria has started to get a hold, and treating the bacterial secondary can help the patient better fight the viral primary.
Not necessarily. Often, treatment and testing can be done in parallel.
In many cases, the treatment is also a test. Every time you apply topical antibiotics to a cut, you’re testing for antibiotic resistance.
It's not "House" where you guess something, provide a treatment, watch as things get worse, then change diagnosis in the real world is it?
The researcher did a follow-up study to confirm their thesis, but I've never seen anyone else follow up on those studies (family with Schizophrenia makes me acutely aware of developments in that field)
https://source.washu.edu/2014/09/schizophrenia-not-a-single-...
oh, would you look at that - a newer study https://biology.ucdavis.edu/news/discovery-hints-genetic-bas...
Merry Christmas!
When enough words, framing, and unstated important premises are omitted, it crosses over from the realm of incomplete or misleading into plain outright lying in my worldview.
They claim "Reverses advanced AD in mice." What they did is reverse symptoms in genetic models.
They claim to "Restore NAD+ homeostasis," ignoring that NAD might not even be causally related to Alzheimer’s, just a side effect. It’s like saying we cured a house fire because we efficiently removed the ashes after the fire. It’s the Tau thing all over again.
The claim: "Conservative molecular signatures" when in reality, 5xFAD mice are poor predictors of human clinical success to such a degree that it’s statistically more common for mice studies to NOT transfer to human biology than to do so.
They also make unsupported claims like "Safer than NAD+ precursors (supplements)," when this is a pre-clinical assumption. No human toxicity trials are mentioned in this context, and there are always MASSIVE differences when switching to real human studies. It might be correct, but there’s no basis to say that based on this study.
Also, the senior author owns the company. The paper has the hallmarks of a "pitch deck" for the drug.
In short, it seems to me that the claim of "Full Neurological Recovery" is misleading to patients. It fails to prove that fixing NAD+ in humans will stop the disease, only that it works in mice engineered to have the disease, and only by assuming that their specific measure is a 1-to-1 with the clinical presentation of the disease. The results are likely the "best case scenario" presented to support the commercialization of P7C3-A20.
Here is the COMMON SENSE question peer-reviews should have asked. Is low NAD+ the fire, or just the ashes?
Why should we believe this works in humans when the last 500 'cures' in 5xFAD mice failed?
Are you regrowing a brain, or just cleaning up a dirty one?
How does one molecule fix five unconnected problems simultaneously? The Context: The drug fixed inflammation, blood-brain barrier, amyloid/tau (protein folding), and memory (neuronal signaling). Drugs rarely hit four distinct biological systems with 100% success....
Where is the toxicology report that proves 'safer than supplements'?
Unfortunately, the moment I saw reference to NAD+ I started looking for this. Thank you.
Please... people, do not get your hopes up over this one PR pump piece released on Christmas Day. This is not a legit study. (It might, perhaps, somehow, still be correct, perhaps... even broken clocks are right twice a day... but it's still not a legit study.)
Broken clocks can be broken in ways that causes them to be up to and including never correct.
;)
Mouse-heifer’s! <knee slap>
Which animals besides mice does this cause a full neurological recovery in?
I used to work with a guy who had been a scientist at a large pharma company (we were both working at a small biotech start-up at the time).
He told me an interesting story... basically, scientists at his company would get an extra year-end bonus if they had worked on a drug candidate that made it past animal studies and into human (clinical) trials.
He told me that one way to 'consistently' get the extra bonus was to work on candidate drugs for neurological diseases (e.g., Alzheimer's, etc.) because ... the animal models for those diseases were (generally) dog shit, so it was easy to find a drug that 'cured' whatever happened to be your neurological disease of interest in mice/rats/etc.
Then you get your bonus and the drug fails in humans.
Lather, rinse, repeat.
Let's hope the cure can be transfered to humans, but I think the chances are extremly low.
https://www.science.org/content/blog-post/lithium-deficiency...
I don’t get this take. Like yes, we aren’t mice, and everything that works in mice won’t work in humans. But loads of things that worked in mice did wind up working in humans, which is why most groundbreaking drugs over the past decades were first explored in mice, which is why we continue to use mouse models.
More than 110 million animals are killed in the United States each year in experiments. I'd rather just accept Alzheimer's than be complicit in this evil.
I understand the compassion for animals, of course, but not this sentence. Advancing science is not "all for fame or fortune". If it cures people, I can see it. I too would love a world without animal suffering, but I'd also love to not be literally seeing (and I just came back from my parents') my dad slip more and more into nothingness at the hand of this stupid disease.