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Dear Doctor, I respectfully submit the following for your comments, and to put a "bee in your bonnet".

 

As we all are aware levadopa certainly has its limitations. It only seems to help with akinesia, and bradykinesia. It can and does worsen other symptoms, and cause nasty side effects. IT has off periods, and with continued use it causes dyskinesia; extreme wiggling. Additionally the dose has to be continually adjusted.

 

After giving the whole PD picture considerable thought I have concluded that the loss of dopamine from the substantia nigra is a coincidental symptom not a cause. Unfortunately the research community seems to have accidentally stumbled onto levadopa in the late 60s, and observed a generally positive effect. They appear to turn a deaf ear to the problematic issues with levadopa.

 

Let me propose an alternate theory. Brain neuron chemistry has several components; dopamine, choline, seotonin, and adrenaline to name some. These chemicals work best when they are maintained in a delicate balance. It is true that PD suferers have diminished dopamine, but nobody seems to be able to quantitate how much. However they blithely proceed to pump us up with dopamine precursors and agonists, paying little or no attention to the other chemicals. Consequently we are just blindly throwing the delicate balance further out of whack.

 

It would be far better to determine the ratios between the neuro transmitters in normal subjects. Develop instruments that can quantitate their levels. Then administer a "soup" of substances to re-establish the natural balance.

 

Furthermore I have a hunch that the absolute level of any one of these chemicals is far less important than the ratio between them.

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I agree with your theory!

 

In fact, we are now beyond the era of dopamine in PD. We are testing drugs that work on the adenosine receptor, on the AMPA receptor, the NMDA receptor, etc to see if the relieve symptoms of PD.

 

We also now know how to use sinemet better...we use it more sparingly now that we did a decade ago.

 

But in some patients, we are stuck...they need more meds and we need to give it to them, otherwise, they become really uncomfortable while waiting for science to find the "perfect balance", right?

 

Great ideas!

 

Yours,

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Thank you Doctor, I am pleased to hear of these new approaches, and agree that levadopa helps some people here and now.

 

Jack

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You are welcome, Jack! To be exact, sinemet helps about 85% of all PD patients. Unfortunately, there is that 15% that never gets a good benefit from the drug. We will do better in the next few years...especially with brains like yours that keep us on our toes!

 

Yours,

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Thank you for the compliment, but it is more "horse sense" than brains.

 

The roughly 85% that are helped by Sinemet; to what degree are they helped, for how long, and what price do they pay in side effects and eventual dyskinesia?

 

It has been my observation that attacking the dopamine issue is at best partial, temporary, and a case of the "devil and the deep blue sea". That is for 85%, 15% are out in the cold.

 

It seems that researchers have been comfortable with incremental adjuncts to levadopa for about 40 years. Even DBP is a dopamine driven procedure. The brain is more than a dopamine factory and needs to be adressed in total.

 

Nobody seems to know the cause of PD, and don't really understand it's mechanistic pathways. Is it even one entity or a bundle of similar disorders?

 

Please, I implore you as a representative of the research establishment to look outside of the box.

 

Thank you Doctor for putting up with our frustration.

 

Peace

 

Jack

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Be patient with me Doctor, I am a skeptic. I know you guys are doing your best within the system.

 

When you said that Sinemet helps 85%, I assume you mean 85% of those that need levadopa, the ones with akinesia and bradykinesia. Dopamine replacement is a coin toss for tremors and does not help the other symptoms.

 

It has occurred to me that what is holding up the research progress is the peer review system for publishing papers. Someone in the past with a lot of clout and respect in the PD research community must have proclaimed that dopamine loss and replacement is the answer. It would then be career suicide to publish outside the paradigm. Meanwhile the patients are losing patience. Push the envelope, think outside the box, challlenge the paradigm.

 

Please go forward!!

 

Peace

 

Jack

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The good news is that your furstrations are finally being heard.

 

As I mentioned, we are now thinking outside the box and looking at various ways to augment the system without going through the dopaminergic mechanism!

 

Yours,

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Of all PD patients, 85% will have a good/convincing response to levodopa. 15% will not have a good response.

 

Of the 85% that shows a good response, about 1/3 of them will have a sustained reponse throughout their lifetime, 1/3 will have a good response for several years then start fluctuating, and 1/3 will only have a short term response for a few years (less than 3-5) and have problems quickly.

 

This was the natural course of levodopa response in one large study. But this was before we learned how to use levodopa propoerly.

 

Yours,

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Dr. Fernandez, you say that 15% of PD patients get no response from levodopa, and that 1/3 of the rest get only a brief response before running into trouble with the drugs.

 

Doing the math, that's a total of 43% of all patients who get either no response or a fleeting one. Nearly half! And this has been the nearly unquestioned treatment of choice for 40 years.

 

Wow!

 

Tom, a caregiver whose wife isn't on dopaminergics.

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This was based on an old study that I quoted only to make the point that there will be a population of patients who will not respond beautifully to sinemet. But the majority will.

 

However, now a days, even if someone has only an initial good reponse to sinemet with a rapid drop off, there is more we can do now. Surgery is a good example. Then we can augment sinemet with other drugs now that we did not have before.

 

If sinemet was the only drug, yes, it looks a little gloomy, but that is no longer the case.

 

I hope this helps a little.

 

Yours,

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Dear Doctor Fernandez, and all the capable, intelligent, dedicated, hard working people of the PD community:

 

I could not help jumping into the dialog again, and I hope and pray none of you take this personally. I find your most recent answer in this topic to be disingenuous.

 

It is human nature to "protect ones position" and I know you all mean well and are trying hard to solve a very difficult problem.

 

However, to say that the new drugs available are a step forward is disingenuous. They are all dopamine prcursors, agonists, and boosters. Even DBP is dopamenergic.

 

Using the numbers you supplied I come up with for levodopa:

 

15% no help at all

28% temporary help with eventual uncontrollable dyskinesia

28% temporary help with increasing of periods as a (f) of time.

28% relatively smooth ride, with side effects.

 

I believe the public should be made clearly aware of these statistics in order to make an intelligent decision.

 

The "new" drugs have their own serious problems as well.

 

I respect all of you for your willingness to fight for us, but please do not sugar coat the truth.

 

Jack

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Dear Doctor Fernandez, this is my second post today in this topic. I hope you read this first because I want to retract the other post.

 

I have decided that I am being unfair to all of you. You are doing your best in a very difficult situation.

 

Peace

 

Jack

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Welcome back, Jack!

 

No one is saying that we should stop development and progress because we are satisfied with our treatment of PD today. We have a long way to go.

 

But there is no denying that people live longer since sinemet was introduced. Of course, some will not respond, as we have repeatedly mentiones, but for those who do, they live longer compared to the days where we only have anticholinergics to offer.

 

To me there is progress when the next drug is better than the one before or offers more choices.

 

When levodopa was first introduced, it provided clear efficacy, but people were getting nauseated. So, carbidopa was placed along with the levodopa giving the tablet sinemet (meaning without emesis/vomiting) so patients tolerated the drug much better. Progress, right? Small, but still progress.

 

Then we discovered that while sinemet can provide good relief of symptoms for a lot of PD patients, some of them develop fluctuations and dyskinesias. Thus, the dopamine agonists were introduced. With these drugs, the dose of sinemet may not be too high and the introduction of sinemet may be delayed thus delaying motor fluctuations. Progress, right?

 

Then we found out that sinemet, although good initially, starts to wear off in most patients. So we discovered "sinemet extenders" such as entacapone, tolcapone, rasagiline, etc. Small progress, right?

 

Then we found out that in some patients, despite all the meds, they have significant fluctuations. Deep brain stimulation surgery was resurrected and is now a generally safe, tolerated and standard treatment for medication-refractory tremor and fluctuations. Another progress, right?

 

We have so much more room for improvement. You are correct that these drugs, like any other drug, including aspirin have side effects. But how many lives, heart attacks and strokes has asprin saved, despite it causing ulcers in some and some being allergic to it?

 

Sugar coating is probably not the term I would like use, but more of giving hope that something is being doing...albeit somewhat slowly for the patient suffering from PD.

 

Yours,

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Too late, Jack.

 

I read your post and responded to it.

 

I am just glad that you are back in the forum.

 

You keep us on your toes! But don't do it too much so we can take a break every now and then.

 

I understand where you are coming from.

 

Peace.

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Guest

Doctor, I have had PD fro 30 years by my reckoning. Officially Dxed in 2001. I have never had Akinesia, and only very mild bradykinesia, a gradual slowing down and very slight difficulty standing up from a soft couch.

 

I do have resting tremors that started in my right hand and have progressed to all four limbs. I have retropulsion, frequent falls (backwards), micrographia, soft monotone voice, depression, anxiety, and nightly "pill rolling".

 

My doctor prescribed sinemet on three different occasions. It did nothing for me, except increase my tremors. I have tried Mucuna with the same results.

 

As you can see I do not have the usual motor symptoms, but do have PD. The tremors and falling are quite aggravating and dangerous. I have cause seven holes in the walls of my house from my falls.

 

Is there a medication(s) that would help?

 

Jack

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I would recommend you see a movement disorders specialist for optimization. Many people with PD have refractory tremor that may need a combination of medications. Some also have symptoms that respond and they don't fully appreciate the response. Any finally some don't actually have PD. I would go to a specialist and get sorted out for you may be suffering needlessly. Good luck.

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Doctor Okun, I respect your education and credentials, but your response is lame and on automatic pilot.

 

I told you I have resting tremors and you suggest a possibility of essential tremor, big misjudgement. You also suggest that my tremors are un-responsive to meds. They respond quite well to Benedryl, but are exacerbated by dopaminergic meds. Lastly, in spite of all the listed symptoms you suggest I may not have PD. You are all in a dopaminergic rut. There happens to be a growing number of PWPs who are distrustful of the establishment for this very reason. They are being prescribed meds that cause dykinesia, leg swelling, compulsive gambling etc.. A multitude of nasty side effects.

 

My question remains, what other than levodopa and its adjuncts can help my tremors, retropulsion, and falling. I expect a well thought out answer, not a "recording".

 

Jack

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Dear Doctor Okun, do not bother to respond to my last post. This topic is causing me and probably you people to have anger. I cannot afford anger, it make me feel lousy, and exacerbates my tremors. For the second time I am going to try and let this crusade go. I still believe in what I say but it is bigger than what I can handle. I feel like Don Quixote. You and the established research community are not going to change until the day comes that there is a paradigm shift in basic thinking about PD. Meanwhile I am going to do my best not to haunt you. I will hide out at MJFF.

 

Peace

 

Jack

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Jack, I am across the planet in Korea at the moment and you made me smile. Good luck on your journey. My main point is to make sure you see a well versed movement disorders neurologist to confirm diagnosis and treatment. Too many times I see referrals where people are suffering needlessly and the medications can be optimized better. If this is not the case for you I apologize. Happy hiding. Keep up the spirit. Sorry, but I felt the need to respond. You have not offended me and you are welcome to continue to read and use the forum.

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Doctor Okun, thank you so much for your nice reply, and thank you for not posting my first diatribe.

 

 

Jack

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