I would appreciate hearing peoples opinions after watching this.
YouTube interview
youtu.be/gxCvbTm699E?si=6eb...
from his LinkedIn page:
Parkinson's Disease Milestone
Jonathan Sackner-Bernstein, MD | Nov 7, 2023
linkedin.com/pulse/parkinso...
Thanks
Just watched. Looks like a breakthrough. Doctor is legit former FDA...
Very interesting. He may be on to something. Good find Roo.
He was interviewed on "No Silver Bullet" last year.
I wanted to hear a fuller explanation of how his theory that we suffering from too much dopamine works, i.e., how inhibiting dopamine production stops the progression. (Maybe he explains that in the No Silver Bullet interview. I'll go back and listen to it again.)
Did you understand that?
Here it is; youtu.be/k703Shlgkhw?si=zQ-...
I think he may be having difficulty getting funding to continue his work
Jonathan Sackner-Bernstein is sole inventor on a patent filing for use of tyrosine hydroxylase inhibitors as therapy for Parkinson’s disease.Nobody else from the scientific community shows the slightest interest in it
There is only one peer - reviewed scientific paper on the subject which is by sole author sackner-bernstein and is just a review and meta-analysis of previous, laboratory research
The rest is journalism
do you know if he is correct in saying that dopamine has not been measured in the cells? I would think they have done that in autopsies.
The problem with this guy is that, dummed down, he says "something", we'll never know what, starts the disease process, and over 10 or 20 years wipes out 80% of dopamine neurons, after which that initiator cause fades away and the damage is done by dopamine.But you are living proof Marc that that doesn't fit the picture. Your disease has progressed with little or no dopamine supplementation,.
Anyone who thinks his ideas are good, stop taking any form of ldopa and report back
Regarding the comment about Marc (not taking levodopa but still progressing). The guy does say:The results using dopamine tissue level data from patients not treated with dopaminergic therapies provide reassurance that the conclusions of preserved and/or elevated cytosolic dopamine levels are not merely a function of levodopa or other dopaminergic therapies and part of disease progression.
From my own personal experience as a caregiver for a decade I can understand and somehow relate to what he is saying. But, I think the real solution wouln't exactly be inhibiting dopamine formation, as it it counteracting it with something (possibly natural) that opposes it. For example: If you guys try some magnesium chloride (the so-called magnesium oil) on the skin at the same moment you take sinemet you would see how much better the medication itself works, and you'll probably stay at a low level without having to increase the dose for quite some time. The chloride form of magnesium in this case works with ldopa synergistically, and makes it perform much better. Movements are better, posture is better, etc.
so would this technique work with mucuna?
I think it should. My experience has only been with Sinemet though.
A leading MDS commented to me as follows on the same paper:
“This isn’t a particularly impressive paper.
Firstly it’s a meta-analysis ie a search of existing literature rather than new original research.
Secondly, it’s no surprise that although total dopamine levels are low due to loss of DA neurones, the levels of DA in remaining cells is normal or high - it’s obvious really.
Thirdly, the entire premise that DA is toxic has little proof and is controversial.
Fourthly, there is no real alternative to driving the remaining DA cells harder to overcome the overall DA deficit to treat symptoms. This is different from protecting remaining cells - neuroprotection is the Holy Grail of PD .
This is not very illuminating I’m afraid!”
My friend really wasn’t impressed at all,
Is he saying too much levodopa is toxic which destroys cells ?
yes, that is what he is saying -- after about 9 months.
NoThat is NOT what he is saying. He is saying too much DOPAMINE, the molecule produced by our own neurons, that is toxic. Of course, in more advanced cases of PD that dopamine was probably produced by our bodies decarboxylation of levadopa. But it is dopamine, not levadopa, which is the toxic substance
right.
His theory fails to explain why mutations affecting the structure of alpha synuclein cause PD.
"His theory fails to explain why mutations affecting the structure of alpha synuclein cause PD." Fair enough. But please explain how you got the conclusion that this is a cause and not a symptom?
Let me see if I got this straight - you want me to explain to you why genetic mutations would not be a symptom of Parkinson's?
Here is my question again. It is about YOUR reasoning, not asking you for explanation of the facts. Just how YOU have drawn conclusions from what you know.
" But please explain how you got the conclusion that this is a cause and not a symptom?"
The reasoning for this is not already obvious to you, it is hopeless to attempt to educate you further.
But levodopa produces more dopamine in the body, does it not? I keep thinking it's name seems to be insinuating "raising dopa(mine)".
Yes it does. So what? I don't understand your point.
Exactly, you don't. Your own point was that Marc is proof that it's not too much dopamine because he is not taking extra dopamine. That does not mean he doesn't already have too much dopamine. I am actually similar to him that mucuna has a terrible effect on my symptoms. So I won't try ldopa because I worry that I might have too much and then it ends up kicking up adrenaline.
I still don't understand your point. How does too much dopamine in the body have anything to do with dopamine being toxic to neurons in the brain. Where does this extra dopamine of Marc's come from. He has had parkinson's disease for a long time and has very few if any neurons producing it.My point was that people like Marc, who have PD and don't supplement dopamine nonetheless progress as fast as those who do supplement dopamine, so it's not really credible to blame dopamine toxicity for the progression. But either way dopamine in the brain not the body is what we're talking about
Not that Marc is going to have dopamine in the rest of his body if he isn't supplementing.
What exactly was the point you were trying to make about dopamine in the body.?
"My point was that people like Marc, who have PD and don't supplement dopamine nonetheless progress as fast as those who do supplement dopamine, " is this something you are certain of? Where can I see this information?
Marc? You can see him at his weekly zoom meeting. Others? Spend a few years on the forum...Oh, you mean clinical trials
And you still haven't explained your point about levadopa in the body
I'm not trying to make a point about dopamine in the body!!! I'm trying to explain that it's important to be open to new information even if it challenges a basic understanding we THINK is certain. And this will be my last comment about it because you and park bear are both not only missing my point, but are trying to challenge some imagined point you both THINK I'm trying to make.
And we are trying to make the point that this theory doesn't fit the facts. Let me make this simpleNever mind if it was faster or slower than with levadopa consumption, prior to 1971 millions of pwp progressed from stage 1 to stage 4 without any dopamine supplementation of any kind, and by definition with very low dopamine levels
This is quite a big clue that something else is responsible. As PB points out, there is a fair chunk of evidence that alpha synuclein is involved in the mix, even though there are several ideas as to how
I repeat. The suggested mechanism doesn't fit the facts
Toxicity happens within other aspects of the body; Allergies come to mind; When excess ragweed is introduced to the body the excess clumps and prevents antibodies from reaching the cell surface.
Whilst he may not be correct in his treatment plan, I'll take anyone who is finally thinking out fo the box regarding Parkinson's. Whilst LD does help some, it has certainly done more harm than good re my PWP who has mainly non- motor symptoms.
Reduce dopamine? I don't get it.
I'm all for research to stop progression. The current bandaid medicines are certainty not doing that. Any success story I have read so far was from people who thought out of the box.
A cure will only be found by trying something different. This guy has done his research and is going through the right channels. I'm looking forward to hearing more.
does anybody know if there are natural tyrosine hydroxylase inhibitors available over the counter to test this hypothesis?
What are natural tyrosinase inhibitors?
The major derivatives of flavonoles, such as myricetin, kaempferol, quercetin, morin, isorhamnetin, galangin and their glycosides, have been identified as tyrosinase inhibitors
I commend him and his thinking ‘outside the box’. I think the PD field could use more people like him. Conventional wisdom has gotten us basically nowhere over the past 50 years.
Good post. My thoughts:1 Good thinking outside the box.
2 Existing neurologists will attempt to discredit simply because he's not one of them
3 my question is that we know dopamine neurons die so there are less of them. So although if he's fòund more dòpamine in individual surviving neurons presumably overall in the brain there's less dopamine.
4 interesting that too much dopamine is toxic
You are so right about your third point. What he is saying may very well be working for somebody in the early stages, but as the disease further progresses it won't do much good. My own personal experience has made me understand that it is the synergistic effect between dopamine and an element that oposes it that really makes the difference in managing the symptoms. Not exactly depleting dopamine completely. And, yes, too much dopamine is definitely toxic to the brain.
If you're in to watching youtube videos, have a look at these: youtu.be/K-Szt6WAs5g?si=QN4...
This link has a link to the core material
I tried emailing a question to him in the address supplied in the above link. But mail was returned address does not exist.
Perhaps try messaging him via LinkedIn?
linkedin.com/in/jonathansb?...
The send button is greyed out when I try to message on linked in.
I emailed him in the past and he emailed me back but maybe the email does not work anymore
Bosco, Do you still have the email address you used ?
From my own experience with PD and treating it naturally with Fava Beans and extracts ....that too much additional ldopa is harmful to the body. I take only a small amount and only when symptoms appear. In that way, I can utilize the dopamine that my own body makes , instead of sending it the message that it is no longer needed. I really feel our body is like the plants I tend...if you chose to feed them chemical fertilizers...they have to have them. It causes a dependancy even though it is upon toxic chemicals. Our bodies recognize the foods God created for our use. It doesn't really know what to do with isolated parts of those foods. Whole foods work to supply our needs. God is Good, look to Him for your nutrition and health. I am stronger at 70 and more coordinated than at 16. Hard work, and good organic fresh foods go a long way in our fight against PD.I am living proof! Aunt Bean
Curious on trying the fava beans. Do they need to be fresh? I'm game to try any foods that help.
thank you
Hi Fava-1 . Can you please help me understand your routine and what regimen you are following that helps you to relieve the symptoms?
Thanks in advance for your help.
AMEN!!! I just started sprouting favas ... would love to know your take on that. Not yet sure how many to eat, but experimenting, and so far on day 3, not much effect. But I do feel a bit more happy.
Don't you need carelodopa to get the dopamine past the blood brain barrier?
Supposedly green tea can replace the carbidopa.
No it can't. And carbidopa doesn't get dopamine past the blood brain barrier
It facilitates levodopa getting to the brain.
Carbidopa is in a class of medications called decarboxylase inhibitors. It works by preventing levodopa from being broken down before it reaches the brain.
Yup. That's not helping levadopa cross the BBB.
But, butFava beans contain ldopa. That's why eating them helps PD
All he has done so far is a literature review. For all of the 'hey at least he's thinking outside of the box' praise, he's no further outside the box than hundreds if not thousands that have gone before him (none of whom discovered a cure for PD either). He just has a better public relations provider (or a bit more nous in this area) and some profile outside of neurodegenerative disease thanks to his career as a cardiologist.
I'd get excited about this when he demonstrates in a placebo controlled trial that metyrosine has a positive impact on PD. And not before that. And unless you are the intercontinental breath-holding champion, I wouldn't do that, either.
hear, hear
"nous" so you're in the UK?
What is "nous"?
I think the British use it to mean common sense.
We've been waiting 60 years for mainstream to produce something new. And...nothing !It doesn't matter how he came up with his theory (Isaac Newton discovered gravity by observing an apple fall from a tree)!
I am sceptical sceptical of him but I'm more sceptical of people who dismiss something without reason. If you've read the material then provide constructive criticism instead of blind cynicism.
Collective research efforts have produced a tremendous amount of new information over the last 25 years, nevermind 60. The SNCA mutation and its connection to PD was only discovered in 1997. LRRK2 not until 2004, less than 20 years ago. There are ~20 something other mutations that have been discovered in the meantime. Future generations will be benefit greatly from these discoveries. The accumulated knowledge around the synucleinopathy family of conditions is actually growing all of the time. Of course, if your measure of progress is 'do we have a cure yet' then you might think we haven't made any. You are free to get excited about this particular piece of work but personally i feel like ive learned how to split hype from promise.
Im afraid Kev that I see the progression you quote as pitiful for 60 years of research. Not a hint of cure, not a hint of prevention, not a hint of regressing. I suspect that the pd field is full of intellectual egos all pulling in different directions. I fear your sense of hype may well be correct but I feel he must be encouraged to play out. If he is a self promoting attention seeker then surely any self respecting pd neurologist should challenge him straight away.
If you don't think the identification of causative gene mutations alongside technology that can edit the germline (which already exists and which the Chinese used to give babies immunity against HIV) offers the 'hint' of prevention then i am not sure what to tell you.
Presumably you have benchmarked this progress you consider pitiful against other diseases of the brain. Since that is what a reasonable person would do, surel.y.
Alzheimers? ALS? Huntington's? Are you satisfied with the progress made on those conditions and is that why you think PD's progress has been been pitiful?
As for self respecting PD neurologists, very few of them would have heard of this guy as he hasn't actually done anything.
I wouldnt compare pd to other conditions. I expect though that they might all operate in the same fashion.None of what you quote has produced any solution to affect the trajectory of a pwp.
If you want to blindly mute alternative theories then go your way but give reasons not blind cynicism.
I wouldnt compare pd to other conditions.
Why not? You literally go on to then say that you 'expect' they might operate in the same fashion. But you won't 'compare' progress? Yet you don't give any reason for not doing so. It seems to me that you are one being 'blindly cynical' about PD research calling it 'pitiful' yet not explaining why.
give reasons
Perhaps you should do the same. I at least offered examples. You've just spoken in vague generalities.
There is great value in looking back at research that has been based on incomplete understanding of original methods. If science cannot question itself, it becomes dogma, which to me is literally the opposite of science. Critical thinking is a key ingredient in thinking outside of boxes imho. And cynicism is an ingredient in critical thinking. But the two are not one and the same, It takes cynicism to think critically, but it also takes a willingness to believe differently than the established norms. I would so love to see that spirit in current "scientific" circles. Instead I see lots of fear and ego. And that is self defeating I think. This guy looked at something that was overlooked. Whether he made a discovery based on that or not, he made a discovery of something key and I think he deserves applause for that in the current atmosphere of dogma and hostility towards anything that questions the basic theories. I mean, has it been established beyond any doubt that we don't have enough dopamine and that is the mechanism? It doesn't seem to be the case...
I'd go with your best examples of mainstream 60 year progress. I.e. no progress affecting the disease progression .
Still not heard a critique of the subject of the post.
Medical industry is profit driven. A cure won't make them long term profit.
It's also not a single monopolistic body, nor a cartel, but a fiercely competitive market, where the big money comes from patentable new medicine and not bulk supply of generics.So the profit motive drives research into being first with the cure.
Moreover a "cure" realistically is not going to be a one-time treatment. Would you reject as failure a one a day pill which halted progress and relieved all symptoms with no side effects but which you have to take for the rest of your life.?
Imagine the profit in being first to market with that
WTP,
You have just written a great truth, which is that those who do research have profit as their main motivation, i.e. making money. This is the lowest of motivations, and in the name of profit, man has always done things that even Satan would be ashamed of. So now I fully understand why it is increasingly difficult to do proper research in order to find the necessary treatments for PD. Bad motivation: profit. And by this, I am not referring to the operators and researchers who carry out their work every day with dedication and a sense of duty, which is the most worthy motivation.
It is not a good idea to associate pharmaceutical research with profit in a post of public relations.
Learn from the master who has even coined a new term, 'The Collective Research,' whose efforts produce a huge amount of new information from which future generations will derive important benefits. Brilliant, I must admit , very “nous -ly”😁
@CuriousMe12 Amen 👍😂I still love the Apple folklore. I once went apple picking with the kids when they were young and they were amused when I sat under a tree. Couldn't get even one to fall on my head 😐😊😂
I believe that the apple falling is historically documented. What is folklore is whether it fell on his head. Either way he was one of the greatest scientists ever. We dont acknowledge him enough in the uk.I like how educate your kids by demonstrating.
Surprisingly, this tree is still growing at Woolsthorpe Manor today and now is over 350 years old. The University of York remains rooted in the present day, but it serves as a reminder that questioning the conventional can lead to extraordinary discoveries.
You should visit and sit under that one day. You may have more luck.
I will definitely do that. Its now in my bucket list
😊
@RooJr Thank you for sharing your research and provoking this quite useful and critical conversation.
Appreciate that this conversation is happening. And thank you Kevin for making me aware.
As a researcher I was taught to follow the data, and the data suggest great promise to this approach. I don't mind people objecting to meta-analyses. I too favor direct research, which is what I propose to do. However, before dismissing a theory because of such an approach, I was also taught to evaluate the related scientific research, which some seem unable to embrace as a strategy. The meta-analysis shows that dopamine excess in the neurons is present, and the next step is to conduct experiments in the lab to test the effects of lowering dopamine levels.
Dopamine reduction therapy was tested by independent laboratories with their data published in first-rate, peer reviewed medical journals. All three labs show that in preclinical/laboratory models of Parkinson's, this dopamine reduction therapy reverses the underlying pathology. Perhaps this approach can do the same for people with PD.
I don't profess to have all the answers. PD is really complicated. Biology is really complicated. And human variability - while wonderful - also makes drug development really complicated.
As a clinical researcher, I participated in the complete shift in the approach to heart failure - even for those with advanced disease - from adrenergic stimulation to adrenergic blockade (the beta-blocker "carvedilol"). I believe the data show this is possible with the use of dopamine reduction therapy, but of course, clinical trials are required to demonstrate that to be so and to teach us how to use the drug safely (the data predict that if a person with Parkinson's were to take the commercially available version at its standard dose, it would be likely to worsen symptoms and potentially be dangerous, so please, please, please, do not try that or a nutritional/dietary supplement).
Let's not reject this hypothesis. I'm focusing on raising the funds to conduct this clinical trial. And I believe we will learn a lot, and perhaps, just maybe, demonstrate that this represents more than hope - a change in your lives.
Are you saying that you are the author Jonathan sackner Bernstein ?If so, good work. I appreciate you will have as yet many unknowns as you work through. But do you have a theory as to why taking levodopa improves our symptoms, if we already have too much ?
I too would be very curious 😜 to know the answer to that question. And would totslly volunteer for a study. And I have not yet taken any medications. Nearly 2 years post diagnosis.
Yes, a quote:
“Scientific accuracy has nothing to do with the prejudice that leads some types of minds to look with disfavor at any observation that has unusual characteristics; skepticism deserves, in this case, the same contempt of naive credulity. “
(Jean-Martin Charcot)
Another one, I think very relevant:
"If you do not have a proven treatment for certain illnesses, bid your time, do what you can, but do not harm your patients."
(Jean-Martin Charcot)
“A great clinician considered the father of modern neurology…”.
“to each their own”…Gio
web.archive.org/web/2013121...
IMO this one above is a very interesting reading about when medical research was a service to the sick.
/
“….Charcot is just as famous for his influence on those who had studied with him: Sigmund Freud, Joseph Babinski, Pierre Janet, William James, Pierre Marie, Albert Londe, Charles-Joseph Bouchard,Georges Gilles de la Tourette, Alfred Binet, and Albert Pitres. Among the doctors trained by Charcot at the beginning of the 20th century account the Spanish neuropathologists Nicolás Achúcarro and Gonzalo Rodríguez Lafora, two distinguished disciples of Santiago Ramón y Cajal and members of the Spanish Neurological School.
Here's my fear. Taking C/L long term, as directed, will somehow exclude me from some future discovery.
How can we apply this finding now... Without causing more damage?
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