[imark3000]

Parkinson's Disease: Why Dopamine Replacement Therapy Has a Paradoxical Effect On Cognition
ScienceDaily (June 16, 2011) — Dopamine replacement therapy, which is used to manage motor symptoms associated with Parkinson's disease, can, at times, adversely affect cognition. Dr. Oury Monchi, Ph. D. in neuronal modeling and Head of the Neurophysiological and Neuroimaging Research theme at the Centre de recherche de l'Institut universitaire de gériatrie de Montréal (IUGM), which is affiliated with the Université de Montréal, and Dr. Penny A. MacDonald, Neurologist and postdoctoral fellow in Dr. Monchi's laboratory, have identified the reasons why within the framework of a clinical study recently published in Brain: A Journal of Neurology.

[olsen]

Hi Imad, this study involved way too few people. might be great spring board for larger study, but as a stand alone study,proves nothing.

[imark3000]

Originally Posted by olsen

Hi Imad, this study involved way too few people. might be great spring board for larger study, but as a stand alone study,proves nothing.

I agree but I find it strange that not enough is known about the side effects of the "golden standard" therapy of dopamine replacement after nearly 50 years of use.
My personal experience of using sinemet may illustrate the point. While sinement helps to some degree to relief my pd symptoms, it gives me serious problems in breathing and speech which could not be explained by the doctors.
Thank you.

[Conductor71]

Originally Posted by imark3000

I agree but I find it strange that not enough is known about the side effects of the "golden standard" therapy of dopamine replacement after nearly 50 years of use.
My personal experience of using sinemet may illustrate the point. While sinement helps to some degree to relief my pd symptoms, it gives me serious problems in breathing and speech which could not be explained by the doctors.
Thank you.

Hey there,

Imad, I was toying with posting a similar citation but wanted to substantiate first. However, I just want to nip the old pro vs. con or Sinemet good vs. Sinemet evil argument in the bud because we are missing the point. I think this article says volumes about what is wrong with the PD Machine (what I think of as scientists, doctors and lack of any real innovation or change in outcome for patients).

This article targets what many of us have written about here many times before? Why do we have nothing but crude form of dopamine replacement as therapy for the last 50+ years?

We do not have a dopamine deficit disorder! In fact we have 60-70% of our overall brain levels of dopamine intact!!!! We lose 80-90% from one small area of the brain- these are the striatal dopamine neurons in the substantia nigra impacting mainly our motor function.

The other dopa neurons are in the Ventral Tegmental in the middle part of our brain and control our reward center and limbic system including the amygdala. We retain those neurons. In fact these neurons are shown to be resistant to alpha-synuclein!!!This has been known five years now...

http://www.sciencedirect.com/science...69996106000933

The bigger picture:

Why in the world has there been so little research based on this? It may potentially answer why our striatal dopa neurons are so vulnerable to attack from alpha-synuclein aggregation thus answering one of the big mysteries of PD.

We do not lose nearly all our dopamine neurons! My God, how confusing and plain wrong; it is misinformation that needs to be corrected and stop circulating.

PD should be looked at as neuron dysregulation disorder or neurotransmitter imbalance disorder --it is about dopamine only to extent that it impacts neurotransmission and chemical balances period. NIH! Someone please address this and start changing that misperception that this is an old person's disease!! Hello, if this were the case why are only striatal dopa cells vulnerable to aging?

Do we need any more "proof" that much more research needs to be directed at alph-syn. It is just plain inexplicable that inside our brain cells are dying due to over-expression a protein and in a neighboring area we have dopa cells resistant. It doesn't take the second coming of Einstein to compare regions in autopsies of PWP. In autopsies, over all this time, no one has ever noted that many dopa cells do not die in VTA let's compare them to the one's here in the SN to note differences.

Why still funding research on completely useless studies on OCD and other behavioral pathologies in PD as some sort of mysterious entity or worse yet try to blame the patient when it is drug induced due to an excess of dopamine in our "reward" center.

These are just a few initial questions...but what we should be asking ourselves is not if l-dopa is toxic or causes problems, but why it has taken 50 years for someone to make this "discovery"? I also wonder what this means for newer treatments with neurotrophics like GDNF? Maybe this is w

Please, I am grateful for Sinemet; I think it is far too maligned. If it were delivered differently, we would not effectively overdose the other part of our brain. Ugh.

Laura

[soccertese]

conductor,
i think your're getting carried away. all neurological diseases are difficult to treat, if they were easy we wouldn't be having this discussion. it's impossible to selectively deliver drugs//genes to brain neurons except by surgery and that seems to be the road that research is taking, there have been at least 6 gene therapy trials for pd that have gotten to phase 2 and 5 have failed.
i was in a trial for sumanirole about 8 years ago, a dopamine agonist. in a county of over 1mill, 3 people volunteered. it ain't easy bringing even a dopamine replacement to market because it's very difficult to prove that it's better than existing products.

so complain all you want about sinemet, my impression is R&D ain't concentrating on pharmaceuticals for the very reasons you mention, the "cures" are likely going to be targeted gene therapy, maybe stem cells, but your're talking about the brain with it's many neuron types/functions where any drug(s) is likely going to have side affects, so i will likely be too old to take advantage of the cure. we may be doomed to our suffering, maybe not, but as a society, prevention research should be the first priority.

personally for you, i'd find the best mds you can, even if you have to go out of state.

[lindylanka]

Would just like to drop this into the argument on sinemet, as someone whose sole dopaminergic treatment has been those little yellow tablets, without which I do not function...... after 40-50 years of knowing about this medication and some of the ways it reaches the brain, and what downsides there are, nobody has even approached a truly humane and practical way to drip feed us with levodopa. It has been well known for many years that a low and constant dose will alleviate many problems of PD and prevent the side effects of throwing into an already compromised system a whole lot more dopa than it needs. At best there is duodopa which some may find problematic though it is reported to be a great improvement, at least there is the home made solution of sinemet in orange drink that can be sipped. In between these there are a lot of other expensive medications which cost a small fortune. No attempts to balance neurotransmitters, in fact often no discussion. And an awful lack of imagination..... It is a useful drug that has been wildly prescribed for some, and is not properly understood by some people who prescribe it. There has been a huge information gap at point of initial prescription to new patients. Also a huge amount of fear-mongering that has led to agonists being prescribed just as wildly, these have side effects as bad and in some cases worse than dopa, as they not only undermine the patient physical, but mentally, socially, and in their relationships. I would defend sinemet - it works for me and gives me a better quality of life - on the grounds that is is a very useful drug. But you just cannot ignore the downsides. Nor the down sides to other PD medication.

Have to agree with Laura that evidence to date is point to the fact that there is disregulation rather than deficiency happening, and that dopa loss is just the start of that process....

Lindy