"There is already more than enough dopamine inside the cells. In some ways, using dopaminergic therapies is akin to whipping a tired horse; it helps for a few strides but doesn't affect long-term results."
"Four laboratory studies report that blocking production of dopamine within these brain cells improves cell function and keeps them alive. Such data in the context of this new observation of increased intracellular dopamine establish a new therapeutic path – one that reduces the average level of dopamine in the nerve cells, while preserving the cells' ability to synthesize dopamine when needed."
*"This approach can be tested now by using the drug metyrosine to partially block the synthesis of dopamine within the nerve cells."
"We've lived in the dopaminergic era since the 1970s and that has allowed for millions of people with Parkinson's to feel some improvement in their symptoms. But the disease worsens inexorably. It's time to test a new approach, one based on firm science as highlighted by this groundbreaking publication. The clinical trial to assess the potential impact of blocking dopamine could start this year." Source: prnewswire.com/news-release...
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"Four laboratory studies report that blocking production of dopamine within these brain cells improves cell function and keeps them alive. Such data in the context of this new observation of increased intracellular dopamine establish a new therapeutic path – one that reduces the average level of dopamine in the nerve cells, while preserving the cells' ability to synthesize dopamine when needed."
finally some studies that respect cellular life and its intelligence, a right context!
Interesting question which I believe to be valid. I was just screened for a unrelated trial and they wanted to make sure that my L-tyrosine consumption did not exceed 500mg.
Neuraly. I opted to not do it not bc of Neuraly but bc the site I would be going to is being run by a very nice but failing man who thought it was 2025. I thought he was joking. He wasn't. That's one of many examples as to why I chose not to put my health in his hands. So alas, no trial participation for me at this time. Are you going to avoid L-tyrosine?
I would like to avoid tyrosine, but I am using DopaBoost which contains 375 mg/capsule of N-acetyl-l-tyrosine and still have 2 bottles which I would hate to waste.Also, I am not sure how N-acetyl-l-tyrosine differ from tyrosine hydroxylase mentioned in the article. Hope someone can shed light on that, or I will have to find time to dig up some information.
“Tyrosine hydroxylase is the rate-limiting enzyme of catecholamine biosynthesis; it uses tetrahydrobiopterin and molecular oxygen to convert tyrosine to DOPA. Its amino terminal 150 amino acids comprise a domain whose structure is involved in regulating the enzyme's activity.”
So if metyrosine inhibits tyrosine hydroxylase this would mean tyrosine builds up? So then you wouldn’t want to take it but I assume if you aren’t inhibiting the enzyme you need it to make dopa?
The way I understand it - metyrosine partially blocks the synthesis of dopamine by inhibiting tyrosine hydroxylase (TH) and I am not sure what inhibition of TH mean - does it make tyrosine to build up or the synthesis of it slows down - for some reason I believe it's the latest. And if that's the case supplementing with tyrosine would be counterproductive as it's already contained in many food products and also can be synthesized in the body from phenylalanine.
It converts tyrosine to dopa so if you inhibit it the tyrosine doesn’t get converted so presumably doesn’t get used up. Unless it is used for other processes?
Gosh it seems extremely important to have enough tyrosine then if taking l dopa medications as it sounds like the dopa can be toxic to cells if there isn’t enough tyrosine. But the metyrosine is stopping tyrosine converting into dopa so it is shutting off the body’s natural conversion of tyrosine to dopa. So I assume then you are relying on the l dopa drugs then to supply all the premade dopa that is needed. In that case taking extra tyrosine is surely a waste of time?
Seems to be quite complicated, having major brain fog lately and my head is spinning from the abundance of information, need to find some mindless activity to give my marbles a little break
Important to have abundant L-tyrosine available in the brain, because if not levodopa will be wrongly incorporated into proteins during synthesis causing toxicity:
After reading through this thread I am now wondering if I should continue having my husband take the 1000mg of L-Tyrosine per day. He does take Sinemet, along with the B1, D3, L-Tyrosine, etc... what are your thoughts on this? Thanks!
It makes sense to me! Dopamine is a kind of addictive substance. Once you stop taking that addictive substance, your body reacts violently I may add, but it does get detoxified and doesn't need the substance to carry on with a normal life.
Despe, do you mean that once starting Dopamine it is very heard to be weaned off of it? I forget, your hubby is on a mixture of C/L and mucuna? I'm only on suppliments including L-tyrosine but I will re-research L-tyrosine. I'm treading slowly with the dopamine. I am thinking of trying just a little mucuna but it is early on for me as my symptoms are still very mild and I wouldn't know what was going on (and certainly my doctor would not either) if it werent for my father having PD. I started L-tyrosine as a baby step but maybe I should not have.
Yes, that's what I mean. Once one starts pharmaceuticals, eventually wants to increase his/her dose to get the same result (reading comments and searching). Yes, my husband takes a combination of Sinemet and MP. So far it's working fine.
Restore gold has tyrosine in it and they reckon that they have had people in early stages completely in remission I think. Check out the reviews. And tyrosine is an amino acid found in food and is required for your body to make dopamine so you do need it. But not necessary in a supplement if you get enough in food?
I was taking a product by PURE called Focus Plus prior to consulting with Dr Mischley. She recommended stopping that supplement. It containedGreen tea 120mgVit B6 10mg
"However, studies show that the individual neurons vital for our ability to move any muscle are producing near-normal amounts of dopamine even in the end stages of PD."
The report is about surplus dopamine. The stuff produced by ipsc grafts. It is not talking about levadopa, the chemical which is converted into dopamine. Not "synthetic" levadopa. Not "natural" levadopa (macuna). (they are of course the same thing)
Not levadopa. Dopamine.
Jim, pdc, how does this theory impact stem cells as a treatment option?
Great question. I'm not sure if I am excited or sad about this, but I continue to wonder if much of what we "know" about Parkinson’s Disease is simply wrong...
The exact therapeutic protocol proposed for use in Dr.SB’S prospective ‘proof of principle’ trial/s is not revealed (if yet concluded) but he does mention that he “filed a Method of Use patent and [is] currently working on a manufacturing process to allow for AMPT to be administered once daily instead of the current version that is administered 4 times a day.” Likely dosage clues are provided in an unrelated 2007 study titled, ‘Low Dose Alpha-Methyl-Para-Tyrosine (AMPT) in the Treatment of Dystonia and Dyskinesia’:
"The dosages of AMPT recommended for most clinical trials and the treatment of pheochromocytoma range from 1000 to 3000mg/day, which substantially reduce catacholamine biosynthesis (36% to 80%).
“Since AMPT acts directly on tyrosine hydroxylase, and probably bypasses phosphorylation effects caused by antipsychotics, it is possible that low dose AMPT might have a special benefit in tardive dyskinesia. We report three cases in which the use of AMPT (at 1 gram per day or less) had efficacy in the treatment of movement disorders, which was superior to previous treatments."
It seems to me one more twist in the loop in which modern Neurology has been trapped for decades: more and more complexity and less and less concrete results to improve the daily life of patients.
This is a perception of the Parkinson's world. But it is what I receive in a chat of about 3,500 patients and relatives from all over the world.
I see more and more a strong contradiction between the official image and the reality, a hard reality: the life of most of the patients is not less hard than 30 or 40 years ago from 4-5 years after the diagnosis...
Cholesterol is not so useful anymore since the Huang studies in 2011 and in 2019. Even less so since the 2017 PURE study.
I am not convinced by new horses to exhaust in the next few years.
Sorry to be or sound cynical. But as Bradesen and Perlmutter say in their book on Alzheimer's, after so many years of failed results we have a right to be angry. Stop treating the smoke, we want someone to treat the fire (of the mitochondria).
Everything goes on as if Knekt, Suzuki, Fullard, had not published on vitamin D in Parkinson's or as if Coimbra had not formulated his "protocol" with very high doses of vitamin D and B2.
Or as if Christine, Schaffner or McCaster had not published anything on vitamin B12.
Measuring intracellular dopamine level and so on? Another unicorn quest for the next 20 years?
We are out of time. We want solutions now in this Parkinson's "enterprise" much more costly than the "Manhattan" project for the atomic bomb in World War II or the Apollo XI program to put a man on the moon.
As Dorsey and Bloem reminded us in 2018 with their "Call to Action"....
I’ve the strong suspect that is a matter of wrong dose of levodopa since the very beginning. Ayurveda used mucuna - without carbidopa - with much lower doses of levodopa (from 1/20 to 1/50) for 100s years without any of the long term side effects known by western medicine (but since it doesn’t cure the disease I would call it that way) plus other plants to rebalance the system messed up by too much levodopa
You are welcome, JMR. As you note, a new 'twist' in the loop through the lifeless, never-changing PD landscape in search of tangible solutions may finally open a new horizon... or may simply end in yet another cul-de-sac. An ample dose of cynicism is the natural response to decades of little/no progress and, in this regard, you likely stand among the majority. In fact, in considerations of Dr.SB's present pursuit of patent/licence for use of AMPT and of necessary funding for his proposed "proof of principle" in a forthcoming PD trial, that deep-seated cynicism remains alive and well.
At the core of this latest quest for a PD breakthrough lies the standard, age-old refrain, "none of the treatments in use today slow or reverse the inevitable worsening of the disease." With this grim reality in mind, Dr.SB optimistically sets off "to test a new approach, one based on firm science as highlighted by this groundbreaking publication" with the stated goal, of course, of "halting and/or reversing disease progression" according to his 'Tacking Parkinson's Disease' statement: jsbmd.com/pd
In order to do so (from the the initial PR Newswire report), he cites four laboratory studies that "report that blocking production of dopamine within these brain cells improves cell function and keeps them alive" and concludes that "such data in the context of this new observation of increased intracellular dopamine establish a new therapeutic path – one that reduces the average level of dopamine in the nerve cells, while preserving the cells' ability to synthesize dopamine when needed."
Despite drawing parallels between similar 180 degree shifts in medical 'doctrine' in the past, and despite generous doses of rhetorical fluff, he fails to articulate a clear and convincing hypothesis by which the biomechanics of this "new therapeutic path" will lead to better longterm outcomes for those with PD. Meanwhile, the hunt for the elusive unicorn continues.
I worry about the old adage. "if it looks too good to be true, it probably is"I worry about perlmutter being cited in support. Mostly I worry about not even rats, mice, or monkeys this time. And then...
CONFLICT OF INTEREST
Jonathan Sackner-Bernstein is sole inventor on a patent filing for use of tyrosine hydroxylase inhibitors as therapy for Parkinson’s disease.
Dopamine toxicity is mediated in part thru its interaction with iron, which also accumulates in SN neurons. It's possible targeting iron accumulation / iron homeostasis would also work. It's not known yet what exactly causes the iron accumulation. Hepcidin is mainly produced in the liver, but it is also produced in the brain and may be to blame for the accumulation. LPS stimulates hepcidin production and LPS comes from the gut (leaky gut) - so a round about approach might be fecal transplant. There may be other ways to reduce hepcidin production.
Another potential target is lon protease.
I hope there is more study on potential use of alpha ketoglutarate in neurodegeneration & its effects on iron homeostasis.
Fun fact - MAO is bound to the outer membrane of mitochondria.
ISRIB could fix all this. If it fails I will be terribly disappointed.
the mechanism mentioned here (ISR) is life's preferred way of renewing itself as an organism, that is, through the death of the old organism and the reproduction of a new one. It appears to be a mechanism written by life itself and is well known at the cellular level. In my opinion it can be slowed down a little and niacin acts on this premature aging mechanism. Furthermore, its properties have been well known in the field of mental health for some time.
And, allowing for the blood brain barrier, how does dopamine made in the gut, have any impact on the deficiency in the brain?
Sinemet was a revolution in Parkinsons treatment 50+ years ago, because it enabled dopamine to be made in the brain instead of the peripheral metabolism, including the gut.
Hello, it reminded me of the information of Insulin resistance, there's enough Insulin, but somehow it's not working. Of Joel Wallach regarding Diabetes, two nutrients are, chromium and vanadium.
Just makes me wonder.My wifes assessment by a Geriatrician Doctor to test for parkinsons was to adiminister her with 12.5/ 50 co-careldopa 3 times a day to see if any side effects occurred.
Within 5 days a big positive difference was seen.
The diagnosis was made of Parkinsons so the tablets were increased to the normal 25/100.
Now increased to 4 times a day for what reason we have forgotten.
Apart from some other issues involved in the treatment, I do wonder, if it worked,why wasn't she kept on the initial lesser dose of 12.5/50?
As you say yourself, because it is considered 'normal'. It's in the doctors' guideline, but that doesn't mean it's necessary. Tailored dosage is important. Women usually need half less C/L anyway. Enough is enough, if the medication works!
Medicine was working for first 3 years at that dosage 25/100 but also may have worked at 12.5/50 thus, occurring less associated dyskinesia or dystonia.Was put on 1mg of rasagiline, by MMD, after a phone call consultation with parkinsons nurse, about July 22.
Read about June 23 that Rasagiline increases dyskinesia.
Asked MDD Jan 23 if she could be taken of Rasagiline but MDD thought not because of wife's intermittent cramp in her leg.
Then Read rasagiline should be give at 0.5mg and if it didn't work increases to a MAX 1mg.
Saw MDD this month and it was agreed to stop the rasagiline ( 1 year after I requested it).
MDD never took any notice that after giving my wife 500mg of B3 ( nicotinamide) twice a day and 100g of coq10 once a day, her leg cramps has gone, 7 weeks and still no cramp.
My point is as in Dr Jonathan sacker-Bernstein paper, less may be more.
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