Thanks Peg and all for your posts,

Many good things to consider.

Jean

Th new PD sounds a lot harder to fix than the old one that was located in the substantia nigra and just a neurological disorder. One question I've had is about the two subtypes that have been recognized for some time - those of tremor dominant and bradykinesia, rigid dominant. Some research on these two has resulted in the belief that bradykinesia and rigidity present a higher risk for dementia. Those with tremor dominance often change to rigid/bradykinesia dominance and after this happens, they are also at higher risk for dementia.

Has anyone looked at these two subtypes among the responders with Cere 120 or spheramine? Should it be a component of every trial ? perhaps it even affects the chances of having placebo effect?

in the new trial - can enough people be included to compare subtyes in at least these two categories?

These 2 subtypes we already know about. Genotypes we must wait for. One person who is experienced, has expressed to me that DNA testing isn't everything it's cracked up to be. Are we to put our hopes in waiting another 5 years for cheaper DNA testing that isn't reliable?

In the meantime, I hope the human component, the emotional component involved in this "slow death", the part that can only be relayed by pwp, is exhaustively explored for subtypes, as well as gastro-intestinal, immunological, hormonal, and other accompanying conditions' effects on trial results.

We are taking scientists word for it about the placebo effect. But we are not dealing with pd when we talk about the placebo, we are talking about tricking people, deception, trying to get past their psyches. It has nothing to do with PD in concept. We already know that emotions, stress levels, excitement, positivity, negativity affect pd symptoms and performance.

What are we looking for, for success? What can we do to help this process along?

paula

Paula - excellent points

And to throw in the mix there are people like me who have both tremor and rigidity, but neither is dominant?

Paula raises many important issues. One of them is that it's time to demand more facts about the role of the placebo effect in clinical trials for PD. We've been told for years it is especially strong in PWP because the expectation of treatment can increase dopamine production -- even in our dopamine starved brains and can last for a long time. Many of the phase I trials that showed promising results and then "failed" in phase II have been explained away by the placebo effect. We need more precise definition of what the placebo effects is and how long can it last. Can expecting to get better reasonably bring about the magnitude of improvements that Peggy wrote about and actually last for 2 years? 4 years? 6 years?

Or did she get better because Spheramine worked for her? just as gDNF worked for many of those trial participants in both phase I and II. Both of these treatments have been shelved. It would be difficult to find funding to reinstate the trials after being labeled as "failures." The Parkinson's community cannot afford to let that happen to CERE120 too. Ceregene should do further analysis of the data and also seek, listen to and analyze the experiences of the trial participants like Carolyn to try to determine what really failed -- the treatment or the trial design.
Dr. Michael Hutchinson, one of the trial doctors who supported reinstatement of treatment for the GDNF trial participants, often said -- if you want to know if a treatment is working -- look at the patients. It's a shame he wasn't listened to then.

For listing of recent "Failed" and terminated PD trials see:
http://pdpipeline.org/terminated_thearpy_thru2004.htm

I know everyone is intrigued by my not taking meds, but I now wish I had never uttered those words to anyone. I guess I got caught up in the moment when I was shouting from the rooftops.

I am considering returning permanently to my meds and would like it if no one would mention my stopping again. I hope this doesn't sound harsh, I don't mean for it to sound that way. I just have great fears about anyone outside the PD community discovering the fact that I ever stopped at all.

On to the topic at hand:

I feel that change needs to begin in the clinic setting, and I know this would not be an easy task to achieve.

Peggy, has great points in your reply.

Question: Why are we, as a patient group not categorized…as time passes the PWP may change category, where the PWP is at diagnosis is certainly not where the PWP would be five years later:

Categories would include: I believe Peggy called this a Statistical Formula
1) slow progression with tremor,
2) rapid progression with tremor,
3) #1 without tremor,
4) #2 without tremor,
5) with dynkinesia,
6) with dystonia,
7) with both 3 and 4.
Secondly, why are therapies not trialed/tested by these categories? And there may be other combinations I have not thought of.
I would be at #1.

So, if NTN data was analyzed using these categories, would the analytical results have been different?

Why was UPDRS the ONLY factor examined in the NTN trial? Why?

In a surgical trial, is it possible that the neurosurgeon simply by skill or by luck hit the right spot in the brain?
If this is even a possibility, why is this not examined when the data is analyzed?

Regarding the above that I have quoted from Peggy's reply:
For NTN we had a diary we were required to complete for the 3-days prior to each quarterly evaluation. This diary did not address mood, illness or any other potential factor that may have had a impact on how well our meds worked or how our symptoms manifested themselves during those three days and there was no questionnaire on clinic day that inquired about illness, injury or any other potential factor that may have had a impact on how well our meds worked or how our symptoms manifested themselves over the prior three months. The diary only address when carbidopa/levodopa was taken and whether dyskinesia was present at any time as well as "on" and "off"

Matter of fact, the only clinic I have ever been too that required a “how have you been feeling” questionnaire to be completed at each visit was Univ of Maryland, but then Dr. Shulman is the PD community leader in quality of life and studies this daily.

I had forgotten this, but when I was searching for how to spell Dr. Z's last name for the who I am post below, I stumbled upon this study.

(July 18, 2007) -- (http://hscweb3.hsc.usf.edu/health/now/?p=185)
The Michael J. Fox Foundation for Parkinson’s Research (MJFF) has awarded Robert Hauser, MD, director of the University of South Florida Parkinson’s Disease and Movement Disorders Center of Excellence, $124,996 to identify different forms of Parkinson’s disease based upon patterns of long-term outcomes in patients.

The USF study will evaluate whether it is possible to identify Parkinson’s disease subgroups based on how patients are faring seven to eight years after initial diagnosis. Some patients experience few symptoms at this stage of the disease, while others have problems with thinking and memory, motor fluctuations, mood, parkinsonism (slowness, stiffness, tremor) or autonomic function (blood pressure, urinary and bowel function).

“One of the most frustrating aspects of Parkinson’s disease — for patients, researchers and clinicians alike — is the significant variability in how the disease manifests itself from patient to patient,” said Sarah Orsay, chief executive officer of the Foundation. “The retrospective studies funded under PD Subtypes aim to analyze data already gathered on different forms of the disease. This analysis could yield valuable information with potential to improve clinicians’ ability to treat patients with existing therapies. It could also advance development of new treatments and enable better design of future clinical trials.”

The USF project will tap into two significant clinical research populations in the Parkinson’s field -- the DATATOP (Deprenyl [Selegiline] and Tocopherol Antioxidative [Vitamin E (Tocopherol)] Therapy of Parkinsonism) study and the CALM-PD (Comparison of the Agonist Pramipexole with Levodopa on Motor Complications of Parkinson’s Disease) study.

How will this study be used?

The items in [] were added by me.

Paula asked who am I...I will take a stab at my assumption of what she is seeking and add the following to the post above:

I wrote the following months ago when I attended a CISCRP panel in Philadelphia



I became interested in clinical trials soon after I was diagnosed, October 24, 1994 at the University of South Florida, Tampa, Florida

The USF Movement Disorder Center, through Dr. Robert Hauser, is very involved in clinical trials.
.
I saw participation in clinical trials as a way to potentially help myself,

In the late 1990s I participated in three Parkinson’s therapy trial: Rasagline/Azilect, Tasmar, Remacemide

In 2004 I participated in a trial at the University of Rochester, NY focusing on the treatment of depression in Parkinson’s disease.

In the beginning, in Tampa, I was very naïve about participation in trial.

Dr. Hauser or Dr. Zesiewicz (Dr. Z to patients) simply asked me to participate, I read the Informed Consent…actually I skimmed it, since I didn’t understand the importance of the document.

Today I know full well the importance of the Informed Consent document and process and have spent the last two years working with other PWPs on refining this process with regard to the safety of the patient.

In late 2006 my then movement disorder specialist, Dr. Lisa Shulman, began urging me to have a DBS (deep brain stimulation) done, citing my number of years with PD and my tremor. I resisted for several months. I the Spring of 2007 I received a PDF newsletter by email that indicated the Phase II of a Ceregene trial was recruiting. The trial was surgical and was implanting gene therapy into the brain in the hope to rejuvenate the dopamine cells back into action. I did my research and discovered that Phase I had excellent results.

I join the trial and had my CERE-120 surgery done on June 18, 2007 at Pennsylvania Hospital, Philadelphia (not to be confused with the Hospital of the University of Pennsylvania.)

Even with the aftermath problems that arose post-surgery...Yes, I would do any of my prior trials, as well as my current trial again. Any brain surgery can experience this same problem.

Today I am able to live relatively normal. I drive my car. I do my own grocery shopping. I don't need any assistance of any kind. The only medical issue I have that is troublesome to me is my depression.

never mind...lol...i understand and no problem.

Starting with "(July 18, 2007)," content was added to Post #16.

These passed through my pipeline email:

1: Understanding the placebo effect. Part 2: underlying psychological & neurobiological processes.Howland RH.
J Psychosoc Nurs Ment Health Serv. 2008 Jun;46(6):15-8. Review.
PMID: 18595454 [PubMed - indexed for MEDLINE] Related Articles

2: Placebo response in Parkinson's disease: comparisons among 11 trials covering medical and surgical interventions.Goetz CG, Wuu J, McDermott MP, Adler CH, Fahn S, Freed CR, Hauser RA, Olanow WC, Shoulson I, Tandon PK; Parkinson Study Group, Leurgans S.
Mov Disord. 2008 Apr 15;23(5):690-9.
PMID: 18228568 [PubMed - indexed for MEDLINE]
Related Articles

I would like to thank the regular contributors to this forum for their tireless dedication in the quest to find an effective treatment and ultimately, the cure. I thought the unity I felt on the old Braintalk forums was gone but its back and stronger than ever.

Although I still don't know what my stats were, I was one participant that had a very impressive placebo response. Here's why I think this happened:

Just prior to signing up to be a participant in this trial, I didn't realize how discouraged I had become about the future. There's no doubt I was very lethargic and sedentary and frankly my partner (who I love to death and couldn't live without) was become more frightened and pessimistic as I progressed.

I remember my study doctor making a dramatic statement more than once "Tom, you are the perfect candidate" having one the lowest early advanced motor scores off meds and improving by roughly 40% on meds.

I remember my son at age 10 absorbing the idea of real vs sham surgery and seeing other advanced patients in the waiting room and it broke my heart as I saw the fear in his eyes.

One of the most touching moments of my life was seeing my son's reaction when I told him Dad was accepted into the trial. I called him at his friends house and he dropped the phone ran up the street at top speed and grabbed me, hugged me and told me he loved me.

After seeing how the possibility of recovery affected my family, I wanted it to happen very badly. If Ceregene wants to minimize the placebo response, I think they need to spend more time on the psychological make up of each candidate.

Futhermore, I have no objection to the concept of sham surgeries in clinical trials as long as there is a guaranteed reward for participating. I'm not sure how this could be implemented but I know how much it hurt to watch my son cry when he heard I was in the placebo group and to realize my consolation prizes were two long scars on the top of my head and some lovely parting gifts.

Putting placebo patients through great emotional and physical trauma and taking every precaution to make the experience feel as real as possible does one thing to a clinical trial - it corrupts the results by producing an abnormally powerful placebo response.

Bottom line:

There are people right now that participated in the Spheramine and Ceregene trials who had a very significant response to receiving the real treatment and went from having advanced PD back to early stage PD. It would be shameful if the potential for these treatments never gets realized due to the design flaws that created such a powerful placebo response.