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> Pieper emphasized that current over-the-counter NAD+-precursors have been shown in animal models to raise cellular NAD+ to dangerously high levels that promot

> 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?

juujian 10mo ago
It's a quality of life vs years left calculation you have to make on a case by case basis.
- mmooss 10mo ago
  You can't make calculations without data, and in this case you have none: we have no idea of the effects on humans.
shawnz 10mo ago
Keep reading: > 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.
luma 10mo ago
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.
A_D_E_P_T 10mo ago
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/ 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.
- nkmnz 10mo ago
  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?
  - cyberax 10mo ago
    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.
    - directevolve 10mo ago
      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.
mmooss 10mo ago
It means we have no idea if this would work or how it would work, and discussing it as a treatment for humans is badly mistaken.
banq 10mo ago
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juujian 10mo ago

It's a quality of life vs years left calculation you have to make on a case by case basis.

mmooss 10mo ago
You can't make calculations without data, and in this case you have none: we have no idea of the effects on humans.

shawnz 10mo ago

Keep reading: > 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.

luma 10mo ago

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.

A_D_E_P_T 10mo ago

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/ 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.

nkmnz 10mo ago
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?
- cyberax 10mo ago
  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.
  - directevolve 10mo ago
    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.

mmooss 10mo ago

It means we have no idea if this would work or how it would work, and discussing it as a treatment for humans is badly mistaken.

banq 10mo ago

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