Thank you for this post Dr. Yassine. I agree with your analysis completely _as a scientist_. Science is built upon incremental knowledge gain through the rigorous testing of hypotheses. That approach matches the risk/reward in science: risk is that we come to false conclusions that end up wasting time and money, and hurting trust in science generally.
_As a clinician_ (which I am not, but can appreciate), I would be uncomfortable pushing unproven treatments for all the reasons you say. There are risks associated with these (many of them not known), and may distract from a patient doing the basics (diet, exercise, sleep, etc.)
_As a human with familial history of dementia_, I don't think that my risk/reward equation is the same. I have but one life to live, and every day I am making choices that will impact that life. Not pursuing a potential therapy is a decision itself. This is not to permit a blanket "try anything that might work". You still need to assess the costs and health risks of each intervention. I don't take homotaurine, for example, because the cost of sourcing it is extreme, and I'd rather place my money elsewhere. Taurine is interesting from this lens - the data is mostly mechanistic, but it's a well studied and cheap supplement. I can see viewing this as a worthwhile risk
Awesome post Dr. Yassine. I think you point out an incredibly important nuance in how marketing behind early biology can sometimes be misleading in helping inform proper care.
Like Taurine, I’m curious if you have seen a little hope/promise for Resveratrol? (I’d probably have to eat a LOT of grape skins to feel any benefit from it, haha)
I understand your review, but wonder at what point with wide availability of biomarker tests like serial nfl and ptau217, even gfap why in extreme urgency some notion of science as it is now biomarker precision medicine n of 1 trials in an acutely devastating terminal condition are not being another option? The massively expensive drug company model is surely creaking? Why are Voyager therapeutics and Lexeo slow walking there apoe4silence/ e2 transfection gene therapies? The tie up between money and science ( and the lack golf public funding now) cannot be ignored . The DART model is counter to the evidence based model as it factors in the patient and the *new* level of knowledge , capacity and risk to the patient and risk the patient is willing to assume on critical circumstances as grown competent and keen to learn and know adults. The answer is not pat pat go and die ( not saying your analysis is incorrect re alz801) but precision medicine. The current model needs a shake up. Like ACTUP in the 80s . Please reflect on this. Science is part of sociology despite being a very important and unique truth teller. See Bruno Latour whom I knew personally.
These are complex decisions and n of 1 trials mean switching between treatments and controls
Of course one can take the risk of taking a new drug but thats not the same as a company marketing an unfounded indication based on a devastating disease
An interesting concept may not equate with a good drug
The technologies to deliver genes to the brain are evolving but exciting nevertheless.
I can't thank you enough for your substack. Your explanations of the science are always clear and enlightening.
Thank you for this post Dr. Yassine. I agree with your analysis completely _as a scientist_. Science is built upon incremental knowledge gain through the rigorous testing of hypotheses. That approach matches the risk/reward in science: risk is that we come to false conclusions that end up wasting time and money, and hurting trust in science generally.
_As a clinician_ (which I am not, but can appreciate), I would be uncomfortable pushing unproven treatments for all the reasons you say. There are risks associated with these (many of them not known), and may distract from a patient doing the basics (diet, exercise, sleep, etc.)
_As a human with familial history of dementia_, I don't think that my risk/reward equation is the same. I have but one life to live, and every day I am making choices that will impact that life. Not pursuing a potential therapy is a decision itself. This is not to permit a blanket "try anything that might work". You still need to assess the costs and health risks of each intervention. I don't take homotaurine, for example, because the cost of sourcing it is extreme, and I'd rather place my money elsewhere. Taurine is interesting from this lens - the data is mostly mechanistic, but it's a well studied and cheap supplement. I can see viewing this as a worthwhile risk
I am all for an informed decision. Thanks for sharing.
I am also excited about ALZ-801 as well, really hope it doesn’t get shelved.
thank you Erin!
Awesome post Dr. Yassine. I think you point out an incredibly important nuance in how marketing behind early biology can sometimes be misleading in helping inform proper care.
Like Taurine, I’m curious if you have seen a little hope/promise for Resveratrol? (I’d probably have to eat a LOT of grape skins to feel any benefit from it, haha)
No
Doses used in mice where benefits are claimed are likely toxic in humans
If we take a step back, isolating a single dietary ingredient and giving it in mega doses as a supplement seldom works.
It's a big industry and an uphold battle.
I understand your review, but wonder at what point with wide availability of biomarker tests like serial nfl and ptau217, even gfap why in extreme urgency some notion of science as it is now biomarker precision medicine n of 1 trials in an acutely devastating terminal condition are not being another option? The massively expensive drug company model is surely creaking? Why are Voyager therapeutics and Lexeo slow walking there apoe4silence/ e2 transfection gene therapies? The tie up between money and science ( and the lack golf public funding now) cannot be ignored . The DART model is counter to the evidence based model as it factors in the patient and the *new* level of knowledge , capacity and risk to the patient and risk the patient is willing to assume on critical circumstances as grown competent and keen to learn and know adults. The answer is not pat pat go and die ( not saying your analysis is incorrect re alz801) but precision medicine. The current model needs a shake up. Like ACTUP in the 80s . Please reflect on this. Science is part of sociology despite being a very important and unique truth teller. See Bruno Latour whom I knew personally.
These are complex decisions and n of 1 trials mean switching between treatments and controls
Of course one can take the risk of taking a new drug but thats not the same as a company marketing an unfounded indication based on a devastating disease
An interesting concept may not equate with a good drug
The technologies to deliver genes to the brain are evolving but exciting nevertheless.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11389752/ Dr. Yassine, have you seen this paper?
Thank you for sharing
Going from database mining to risk reduction implications is a stretch
Ezetimibe is interesting but it works at the gut level
I am not sure it enters the brain