I read the following grant abstract (funded by the MJFF) on another discussion list and it raised lots of questions about where the research is heading and if the scientific community is showing signs of giving up on the more advanced PWP. Full text of Grant abstract at
http://www.michaeljfox.org/research_...s_3.cfm?ID=590
Excerpt:
Immunology and Bioactivity of Regulated rAAV1-GDNF in Rodent Models of PD
Program-non- specific Funding 2009
Objective/Rationale :

“Clinical trials with a trophic factor called GDNF, where GDNF is injected directly in the brain by pumps, have not been completely successful. Many scientists believe that the delivery method is part of the problem and have been calling for gene transfer as the most viable delivery method. We further contend that GDNF will only function properly as a therapeutic when used with early stage patients. In order to perform gene therapy in early stage patients, extreme safety of the gene therapy must be demonstrated prior to use in humans. This project is part of a program to produce a viral vector to deliver GDNF but with the added safety that it can be turned off by a harmless antibiotic if side-effects appear….”

Researchers
Ronald J. Mandel, PhD
University of Florida College of Medicine

The data will be used to move the preclinical studies into a phase I clinical trial – for early stage patients only…

It seems we will be forever haunted by how the results of the Amgen GDNF trial were reported (or misreported) – was it a “failure” or “inconclusive” or “not completely successful?” The research on infusion delivery of neurotrophics seems to have been dropped, although further research was called for to resolve the issues in the Amgen trial. . We will probably never know the true potential of this treatment method.

In some articles, there is finally acknowledgment that at least some of the GDNF paritcipants ( many in advanced stages) did improve –“some dramatically”, but the consensus seems to be now that gene therapy is the delivery method of choice.
Seems we’re always going back to square one… maybe that is the way science works, but time is not neutral for PWP.

It feels lately like the funders and the researchers would prefer to just forget about the "lost generation" of now advanced patients . We’re told to take new formulations of levodopa and get a DBS to deal with the dyskinesia caused by the levodopa, as the scientist’s interests seem to be turning to non-motor symptoms.
And now they don't even want us as lab rats.
The proposed phase I clinical trial, using a new viral vector to deliver the GDNF gene would recruit only early stage patients Is the belief that “GDNF will only function properly when used with early stage patients."

Is this generally accepted or does it reflect the opinions of a few researchers? Are they attributing to all the improvements noted by advanced patients in other neurotrophic trials (GDNF, spheramiine, neurturin) to "just a placebo effect?”

ISeems to me there is going to be a recruitment problem for a trial that asks early stage PWP who are likely to be experieincing good results with drug therapies to agree to experiemental brain surgery. Is it ethical in the first place? What is the risk/benefit equation for them?

And should human gene therapy trials be on hold until a gene therapy regulator is perfected ?..
Last summer there were related discussions on PDOnlime Research . see threads at:

http://www.pdonlineresearch.org/resp...able-promoters

http://www.pdonlineresearch.org/resp...will-take-time

http://www.pdonlineresearch.org/rese...ntial-treatmen
t-parkinsons-disease#commentary

Would like to hear opinions of other PWP. Maybe after 14 years with PD I’m just becoming too cynical and and suspicious.

there is a lot I could say here but i am hoping everyone of you reading reply to this post, whether it be to add, clarify,vent - or whatever.

There are several indications that our health care is about to change. And our research money is managed by business people who do not put our welfare first. That isn't their job.

This has morphed from lawsuits and insurance and now the pharmas and biotechs.

They don't care about advanced parkinson patients and are very aware that the baby boomers are too expensive to maintain. Now if that's your thinking , and you are a pd community leader, start looking for a new job. That would be the final ethical breech and it sounds very like obama czar style economics.

It's time for an indepth investigation into conflicts of interest and can someone tell me what leads....uh...Dr. Mandel to contend gdnf only works with early stage.? sounds like the same spin as the claim that freezing and falling are nondopaminergic in advanced patients.

Business is about bottom line. And now it's gone too far. Your silence will be interpreted as acceptance.

well i don't accept either of these "claims"

Do they honestly expect a 30 year old early stage parent of children to risk gene therapy? I would advise against it as a patient advocate.

RISK - everything much sooner than pd would take
BENEFIT - unknown
TREATMENT PRODUCTION - oh is that what they are trying to do? In your dreams.

I will stop there for now .

I actually thought i was losing my mind until a med change worked wonders
This is about money. Everything is about money. THe ethics in the research community is so far over the line that people should be replaced.

Who cares about stress in the advanced? they are going to die anyway.
welcome to the future...
by the way we are hip to distractions we aren't the crazy obsessed ones - we are the brilliant ones with pd;

paula

What the heck is going on? WHY do researchers Ronald J. Mandel, PhD et al want to run a trial with GDNF for people with early stage Parkinson's only?

Why don't researchers set up three trials running concurrently?

1. early stage pd
2. middle stage pd
3. late stage pd

and then see what works for whom?!

And I agree that researchers will have a very hard time getting people with early stage pd to sign up for a gene therapy trial. If a person with early stage pd asked for my opinion, I would recommend against them taking the risk of brain surgery in any gene therapy trial.

I am outraged.

It has always been about money my dear---except for the eelemosynary (charitable) orgs. Suggested amendment to the Health Reform Act---Appoint another czar to oversee the actvities of these tax avoiders who are now apparently ready to reinvent the death panels. Maybe I should stump for an appointment? Bob C

Bob,

You really need to work on your spelling....it's eleemosynary......


paula

i wouldn't get that upset. economically, drug companies will have to attract every pd patient they can get if the treatment gets fda approval. a researcher obviously doesn't realize that early stage pd'ers will be very reluctant to risk brain surgery when they can do ok on drugs. neurologix took over a year to find 44 candidates for their gene therapy trial and it was certainly less dangerous operation than a dbs. my point is it's very difficult to find candidates for any pd trial.


the bigger issue is how do you show a statistical significant improvement in early stage pd'ers? how do they define "early stage"? honestly, i imagine they would take any healthy individual, they certainly want people that are going to live at least 5 more years, don't have other serious medical conditions and are healthy enough to undergo surgery.

that said, make sure you have an extra birth certificate.

... fewer than 1% of pwp participate in clinical trials ...

the bigger issue is how do you show a statistical significant improvement in early stage pd'ers?

I'd never see my self as any kind of scientist, but even my non-scientific mind has wondered a lot over the years about treatments that are aimed at being neuroprotective in any way - what are the predictors of the future.... and how do you measure them, and what about the ....... placebo effect, and then again in early stage how do you have any indication of rate of progression, so what exactly are you measuring, are you even sure that tremor or that stiffness IS pd, and what are the symptoms you are trying to deal with - and exactly at what point do you designate any stage as progression, as far as I can see most of it is arbitrary and based on subjective observation.....i could go on but won't, as i said i am not a scientist, but logic and ethics are something i am very interested in and a lot of this does not seem to fit into those criteria, only money and some more please........... for goodness sake half the time they do not even know whether or not they are actually seeing pd, and it can take them years to make up their minds........... it all seems like singing in the wind ........the money is made on our hope, and something needs to give, they need to hear us because we are more than the molecules that make us, and there are those among us who need to be cared about now, and listened to.

i am feeling mad about things too, recently saw a film about dementia, you could easily spot the different types, and the difference good care and fewer drugs can make to QoL for elders, they are in this too, and when a figure of less than 1% of PwP volunteer for trials, (apologies Jean, please take it as i mean, you are right to say the US situation) i cannot help but think of those around the world who never even get a diagnosis, and those who do, but never get a simple medication that will help, and where is the 1% there, in the places where people are desperate, because they are too old, too poor, too uneducated, or too much in the wrong place. Nobody is talking about QoL for all - everyone, dealing with every disease entity is looking for a cure, and it is my belief that very few are looking for it, they are too busy setting their corporate agendas....... on the other hand maybe they will just look for older early stage.......which will go right against the global projections for pd increase in the near future.... sorry for the cynicism, tonight it feels a good antidote to unrealistic hope....

Excellent question, Linda.

I often wonder if the stage is a factor in the response any current trial patient has with the therapy.

Just as I often wonder if the neurosurgeon, who has to find the target, is a factor too.

Carolyn

I hear ya, Linda, et al replying to this thread.

And paula said: There are several indications that our health care is about to change.

Do ya think?

I explained my theory on this one in another thread, so I will link to it. http://neurotalk.psychcentral.com/thread110038.html
If you want to bring it into this thread, be my guest. Here's a synopsis of what I tried to explain in more detail elsewhere:

I believe our research community has finally realized that we have been using modes of measurement for PD research that are useless and give us no feedback as to how a therapy is working.

The reason behind my somewhat shallow theory is very deep indeed. Dopamine therapy does not wash out of our system for a minimum of 2 weeks, which can vary person to person due to what one had to eat the night before, his/her metabolic rate, body fat, if we have any other ailments requiring the use of our central nervous system, how much energy was expended prior to the testing, whether or not the patient had ample sleep, our mood, whether or not our bowels have been moving regularly, if we have been under any stress lately, what medications are stilll in our system, and don't forgoet this one - the placebo effect - i.e. how we THINK we are feeling.

In other words, and strictly my opinion, what scientists have been measuring for the last forty years is the rebound effect of having been on carbidopa/levodopa therapy, or what we call so sincerely dopaminergic therapy.

Linda, (and Jean - this would answer your question, also)- I believe the researchers are trying to redirect attention to this fact by the call for recruitment of "those who have NOT been taking dopaminergic therapy." THAT would be a much better evaluation of whatever therapy was tried. And of course, you cannot abruptly stop the dopaminergic therapy (they usually say 12 hours offo meds) with a PD patient WITH dopamine in his/her system, or the result could be lethal, resulting in Neuroleptic Malignant Syndrome.

Defined by the NINDS website as:
Neuroleptic malignant syndrome is a life-threatening, neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs. Symptoms include high fever, sweating, unstable blood pressure, stupor, muscular rigidity, and autonomic dysfunction. In most cases, the disorder develops within the first 2 weeks of treatment with the drug; however, the disorder may develop any time during the therapy period. The syndrome can also occur in people taking anti-Parkinsonism drugs known as dopaminergics if those drugs are discontinued abruptly.

Additionally, we haven't proven just how "advanced" Parkinson's looks. Are we measuring the symptoms of the disease, the side effects of the dopaminergic medications,, or the rebound effect of being off meds for at least 12 hours?

To quote paula, " They don't care about advanced parkinson patients and are very aware that the baby boomers are too expensive to maintain." I'm not sure just who "THEY" is, but there are 80 million of us babyboomers. Do you think that many making noise might get some attention? I DO!

"They" had better get to work on management of the advanced PD patient - there are 80 million (if the theory holds that 1% of the aging population gets Parkinson's, that is still 8 mil . . .. oops! corrected below. Make that 800,000 ) who are knocking on the doctors' doors as we speak.

I went to bed and sat straight up thinking - 1% of 80,000,000 is only 800,000!!! I hope I corrected this before any of you caught that! (I was an English major lol)
Peggy