One thing that nags at me.

Most of the PD research I've seen focuses on the LEVELS of dopamine in the blood stream (and protecting the cells that produce it), under the assumption that this is an imprecise but statistically valid measure, however imprecise, of the level of dopamine in the brain itself. (due to difficulty in directly measuring dop. level in the brain.)

However, I have seen very little, if anything, on the regulation of the flow of dopamine within the brain as a mechanism to control & "smooth out" body motions.

i.e., (I think reverrt123 put it this way, years ago): "the fast, hard hammer slam of PD, and long, slow fade."

So, what IS the mechanism the body uses to:
1 sense/ detect the need for more dopamine to communicate to the body that particular parts need to move?

2 accurately calculate the amount of dopamine needed by the brain to most effectively communicate this need to move to the body?

3 .. and finally, actually deliver the dopamine calculated to deliver the movement message to the appropriate movement controlling sections of the brain?

All of this is perhaps a long winded way of saying that I think PD is not JUST about how much dopamine we have, but also, how well is the dopamine storage/ regulating & dispensing system working?

BTW, I posed this question about dopamine regulation & dispensing to Dr. Michael Okun (considered to be one of the foremost PD docs globally), as well as:
what does taking Sinemet do to a person who doesn't have PD ("nothing," it is said, further indicating the importance of a dop. regulating/ dispensing mechanism)

... and what would it be like if a person had absolutely no dopamine whatsover.

His basic answer was: "you are a deep thinker.. and we have no answers to these questions." While I may enjoy being called a deep thinker, frankly I would rather find that my questions led to fruitful research in dealing/ managing PD.

... oh, and when I shared my experience with laughing gas at the dentist dramatically reducing my arm tremor, his reply was something like "we've known for quite a while that sedation works to lessen symptoms of PD."

OK.. then what about making it legal for PWP to have their own bottle of laughing gas, or developing a sedative that lessens PD symptoms without putting a PWP to sleep?

Perhaps these questions simply reveal my ignorance of the complexities of PD, ... or perhaps my wondering "what ARE these guys working on as researchers if they aren't following these valuable PD clues?" has some basis to it.



George

IT'S obviously trial and error and a moving target.
think about it. a non-pd'er can eat a 2lb steak, with likely ounces of dopamine precursors in it yet that person doesn't have any central nervous system problems.
conversely, a healthy person can fast for 30 days, not eat any protein, and doesn't develop pd symptoms, either your brain is recycling dopamine or it is breaking down muscle to get precursors. then think about how you can get a similar benefit from 12mg of requip as you can from 600mg of carbidopa/levodopa, which tells me very little ingested l-dopa actually gets to the brain, have to wonder how much of that 12mg of requip gets into the brain?
i guess my point is a healthy brain tightly regulates the amount of dopamine floating around in your brain, only makes as much as it needs. with pd dopamine synthesis is reduced as brain cells die or become damaged, maybe surviving cells make more, maybe other types of neurons make dopamine. it appears the dopamine breakdown in the brain still works since we have to take it so often.. my point is even if they had the info you asked about, not sure things would be much different. you can't selectively distribute an oral drug to just specific parts of the brain. but you can selectively insert stem cells or genes which is when imho that info becomes really important.


the holy grail is a long lasting l-dopa pill that will provide a constant blood level of l-dopa, still have to becareful about when you eat protein. impax labs is awaiting approval of their improved extended release pill, there's the neupro patch and 1 a day requip. and the duodopa pump, a cheaper l-dopa pump using an insulin type pocket pump is under development, there's subdermal plastic rods under development that have a months worth of agonist. my insurance doesn't cover any of these newer products. and DBS which just works, who cares why?

Thanks for your well formulated ((pun intended) reply, soccertese (Socratese tease?)

While in general, I agree with the view thatt often times "understanding is the booby priize" in the Game of Life, my sense re the content of your comments is that the area of dopamine regulation in the brain MAYA BE a fertile area for researchers to explore.

Think about it: if the mechanism that regulates dopamine levels in the brain is clearly, unequivocally identified, then the next step could be: "tweaking" the regulating mechanism, so the brain itself makes more efficient use of the existing dopamine (whether produced by the brain itself, or introduced chemically)

I don't see this as any necessarily any more dangerous than DBS, or taking
what (at least for me) is in essence a powerful stimulant (Sinemet).

Simply another research path to explore, and as you pointed out, what counts is finding treatments that work better for more PWP. Who cares which research path develops them?

Right now, taking Sinemet is akin to throwing a bunch of mud at the wall, hoping it's not too much (causing dyskinesias) or too little (meaning not going ON/ being OFF)

I totally agree with you re: the need to look at the costs of treatments, whether they be chemical or "procedures", i.e. DBS.... not only $ wise, but also psychologically, emotionally & et all. As PWP know, the price of each path can be high.. (nicely called "side effects" by the medical folks)

Just my 2 cents.

George

keep in mind that oral dopamine doesn't enter the brain, THE BRAIN IS DESIGNED TO KEEP DOPAMINE OUT, YOU DON'T WANT DOPAMINE ENTERING ALL AREAS OF THE BRAIN WHERE IT IS LIKELY POORLY REGULATED and why it is broken down so rapidly, i imagine the brain is designed to destroy or sequester dopamine where it shouldn't be. that's why we take l-dopa, it passes the BBB. that's why gene therapy, stem cell research target specific areas of the brain. you don't want GDNF in the wrong place.


we don't produce enough of our own dopamine, the regulation is mainly by cells that are no longer functioning, the goal is to restore those cells, replace them, insert genes into other cells that will at least produce dopamine, etc.

i don't think researchers would be developing these complicated and expensive procedures if they didn't understand dopamine regulation.

OK.. then what about making it legal for PWP to have their own bottle of laughing gas, or developing a sedative that lessens PD symptoms without putting a PWP to sleep?


DEfinitely would say that laughing gas should not be used by PwP. not recreationally or medicinally unless absolutely neccessary.

My reason for saying this. There is news that Folate could be implicated in the mechanisms of PD. Folate and B12 in the body have a sort of binary relationship in something called the methylation process, they are to a large degree dependent on each other, and there are several other substances in the body that also interact to get activity in the mitochondria. Most of this work starts in the stomach, and becomes part of a continual process the body is engaged with.

So why no laughing gas? Because it can catastrophically interrupt the B12 cycle, and thus interfere with these complex processes. Damage a part of the process and things unravel. NONE of this is really well understood, and its hard to know what is most important, but with studies implying folate could be a facto, I would not take a risk.

People can have genetic methylation defects that are fairly common. All in all not something to play around with, especially if you have PD.