In the effort to learn as much as possible about the cancelled GDNF study, Grassroots Connection (GRC) editors have been communicating with me about my participation in the GDNF study.  I have had PD for 17 years and first noticed symptoms in 1987 at age 36. I was diagnosed in 1988.

Back then, my children were ages 3, 5 and 11, and I was working full time as a meter reader for a utility company  - a very physically active job performed mostly outdoors. Now my children are 20, 22 and 28, and I am on Social Security Disability.  PD has had a profound effect on my family life and career. 

However, I believe that life does not stop with a chronic illness, and, with faith in God and a great group of positive, supportive good friends and relatives, I make it a priority to retain a positive attitude and despite PD's limitations, stay as active as possible.  I find therapy in writing poetry and sharing it with others and have begun to facilitate a Young Onset Parkinson’s Support Group.

THE  SURGERY

I was accepted as a GDNF study participant on July 25, 2003.  I was evaluated and given many tests, including MRI’s,  a PET scan, x-rays, blood and urine tests, physical, mental and psychological tests.   On November 5 of 2003 I had surgery to have the pumps, tubing and catheters installed. Two pumps were implanted into my abdomen with tubes running under the skin from the pumps to behind my right ear and attached to the skull.

While in recovery, I experienced severe dyskinesia until the surgeon ordered reduction of my Sinemet dosage.  Later, I briefly demonstrated a side effect known as transient Lhermittes signs, (a mild tingling down the arm).   During the nine months following surgery my symptoms did improve slowly; my children noticed the improvement more than I did.

THE GDNF STUDY - Consent Forms

Over the course of the GDNF study I was asked to sign several consent forms. For clarity, I have listed the dates and time frames covered by the forms.

“Pre-surgery stage” : also referred to as pre-clinical stage.

Two months of testing and evaluation; three day hospitalization after surgery.
 

“Double blind stage” : 1/2 of group received placebo for six months.

Included a chart of detailed, scheduled, pre-arranged testing for each visit and risks through the first six months in the consent forms signed on 07/25/03

“Open label stage”:: all participants receive GDNF; signed 4/21/04.

Included was a chart detailing all scheduled testing for each monthly visit for 24 months.  The visits were scheduled 28 days apart to refill the pumps and for testing and evaluation.

After the study was abruptly ended on 09/01/04 :

“Post treatment” stage": consent form was drawn up and signed 3/30/05.

Included a chart showing 12 scheduled monthly visits beginning on the 09/01/04 date. Actual post treatment visits did not occur on 9/01/04, but began on 3/30/05.

Later, the forms signed 3/30/05 were replaced by:
   

“Post treatment” stage": consent form signed 06/22/05.

Included a chart detailing 24 scheduled visits back-dated from the end of the study on 9/01/04 to end in October of 2006 unless extended.  This shows the first six visits occurring monthly and the remaining visits to be scheduled every three months.

ANTIBODIES 

Amgen listed two safety reasons for ending the GDNF study.  The first is:

• the development of anti-r-metHuGDNF neutralizing antibodies in five patients;  I was identified as one of the five with these antibodies

No one wants a war of neutralizing antibodies going on in their head.  But, by the same token, no one welcomes the symptoms of PD.  It was a risk we chose to accept when we offered our bodies and lives in search of answers and accurate scientific data.

On 10/05/04, I was assured by the doctors that no adverse effects from the neutralizing antibodies were evident to date. However, I was told the neutralizing antibodies would always remain, either actively or dormant.  Later on, the study coordinator informed me that a blood test revealed no neutralizing antibodies.  Now I’m waiting for word from my doctor about whether I can ever be treated with GDNF in the future.

Having been informed about the halt on 9/01/04, and then about having neutralizing antibodies on 10/05/04,  I became increasingly concerned and was anxious to have the pumps removed. They were very uncomfortable, sometimes painful. The area behind my ear where the tubing was close to the skin surface constantly itched. I may have chosen to postpone its surgical removal (in the hope that GDNF might be restored) if I had known the neutralizing antibodies were no longer present. 

Catheter Dislodgement

When my pumps were removed, it was found that one of my catheters had become dislodged. 

I was left wondering about others having both dysfunctions (detached equipment and antibodies) and if anyone was investigating the effects of the dislodged pumps on the performance of the drug and results of the trial.

CEREBELLAR   LESIONS

In the “open-label” consent forms signed at the sixth month transition visit on 4/21/04, there were additional risks that we were required to be informed about and sign to accept.  One of these risks was that some of the monkeys had developed lesions in their cerebellums. This same monkey study later became one of Amgen’s reasons to halt the study.  However, as with the antibodies, there are many doubts and unanswered questions regarding this "safety" factor:

• The monkeys received a much higher dose than the human subjects did.

• The clinical trial investigators involved in the study are not in agreement about the cause of the lesions; some attribute the lesions to the sudden withdrawal of the high dosage, not to the GDNF itself.

   Why did they require us to sign documents accepting this risk and then use the threat of the lesions as a reason to discontinue the trial?
       

Efficacy

The third reason given by Amgen for the GDNF study halt in September 2004, was that after six months, the GDNF study failed to meet its primary endpoints.

I can only speak for myself about this, as I have not been provided with Amgen’s results of the GDNF Study.

·         I did not get the placebo.  My symptoms improved slowly and the improvement was seen by my children more than by me. Improvement was most notable to me in the cognitive area.
 

·         On post-treatment Neuropsychometric testing, which measured cognitive reasoning and memory, my performance on a test that involved addition of random numbers improved significantly. On the pre-test, I was unable to complete the first tape; during post-testing I completed two tapes and some of a third.
 

·         The progression of my disease has been slow.  It seems logical to me that regeneration of my cells conquering the 80% barrier alleviating my symptoms could easily take longer than the 10 months that I was on GDNF, particularly taking into consideration the potential effects of the antibodies and the dislodgement.  Add to this the well-known fact that there are such a variety of responses to treatments among people with PD, and 10 months hardly seems long enough to reach an accurate conclusion about efficacy.

The larger question regarding my progress is: How much did the dislodging of my equipment affect my outcome?

Your pump was turned off in September 2004 but not removed until June 2005. Why such a long wait?

The post-study treatment was delayed while a new consent form was written.  The GDNF Study coordinators called me several times, informing me that they were trying to make sure the wording in the contract protected me and my rights to follow-up treatment.  Consequently:
 

• For six months after the halt of treatment, I did not receive any medical monitoring of the neutralizing antibodies, even though the presence of antibodies was labeled a safety issue and one of the reasons for the trial halt, according to Amgen.   

• The location of the catheters was not monitored during that six-month period from 9/04/04 to 3/30/05;  I am still waiting on word about when my catheter actually became dislodged.

You were one of the patients whose pump/catheter became dislodged. Do you know of other patients this happened to? What can you tell us about the dislodgement?

I understand that I was one of five out of 34 patients in the GDNF study whose tube/catheters had become dislodged, but no information was provided about when the dislodgement occurred.  After removal, it was reported that one of my tube/catheters was correctly in place but the other one had become dislodged and was "barely hanging on the edge.“

Do you regret participating in the GDNF trial and would you volunteer for another trial someday?

An unexpected difficulty for me, was the feeling of not having control over what was happening to me. I feel confident though,  that some form of GDNF or a similar compound could be the answer we have all been hoping for.  For me, being in this study was a successful experience because I was able to contribute to the knowledge about GDNF and I still feel this procedure could help those who are willing to accept the risks.

I have no regrets about participating in the GDNF trial and appreciate the medical investigators for their expertise and professional care.  I still believe that research is the key to finding a cure.  The need for active participation in clinical trials is great. I was inspired by my need to participate.  There are 1.5 million people with PD and 40,000 more are diagnosed each year.  I ask for support in helping to solve the mystery of eradicating Parkinson's disease.
 

Copyright © 2004-2009 Parkinson Pipeline Project.

All rights reserved. Revised: 12/11/09.