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Thanks to all the posts on this! great info! great links! it generated a bunch of questions. I don't know which or who or if any of you has answers to them. but here they are:

Just want to make sure I understand Jean, Perry & LindaH:
There are three GDNF trials coming up?:
ONE: at NIH with Dr Federoff and Dr Russell Lonser phase I/II
Invasive injection of GDNF in AAV virus into the Putamin.
To make a “stable baseline assessment” starting point – were:
1. 6 months data by an at-home measurement device by Kinetics
2. clinical Neurological exams
3. neuro-psychology tests
4. dose level tests
5. approx number of patients?
6. projected length of trial?
7. will there be follow up assessment after trial ends
8. if so for how long?
9. will there be any data comparison with previous and
Concurring GDNF data now or planned for?

I don’t understand the definition of surgery if this is an injection.
1. Unless they must open the brain to see where to put the needle?
2. And are the dose levels to be given to different people or
3. are they all starting at a low dose and some give more in time?
4. Are the “Subsequent surgeries “ refered to,
to increase the dose level?

TWO: in Bristol, UK with Dr. Steven Gill phase II
Direct infusion of GDNF Molecule
1. Baseline Basis to be used? 2. same as above? 3. dose levels? 4. approx. number of patients 5. projected length of trial? 6. same ? as above 7. same ? as above 8. same ? as above

THREE. BC, Canada, MedGenesis Therapeutix Inc., Dr. Eric Mohr, phase II, Convection enhanced delivery of Amgen’s GDNF protein to brain. Same 7 ?s 1. this trial to prove safety & benefit to do 2 bigger trials 6. 18-24 months

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here is a paragraph of info i copied from the MJFF article listed by Linda H that I thought was particularly interesting:

jingle belle/April C.
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We have developed a novel approach to delivering GDNF to the putamen by a process called convection-enhanced delivery (CED). This approach is aimed to optimize drug distribution within the putamen while minimizing exposure to drug in other areas of the brain. The approach integrates the use of four distinct components: a customized, implantable catheter system for convenient repeat treatment at the neurologist’s office, a specialized surgical planning software for optimized catheter placement, magnetic resonance imaging (MRI) technology to visualize the actual drug distribution in the putamen, and a new intermittent dosing scheme for optimized delivery of GDNF. Upon final testing in animals, our approach is scheduled to be studied in patients with Parkinson’s disease starting in 2011.
Per MJFF article 2010

Beginnning with why has it taken 3 years to get it together? Perry has asked Federoff so many times when they were going to s tart and it was always this fall we hope or this spring we hope.

i don't know how many there are

they are not all gene therapy
their is also an encapsulated one being worked on
it is a surprise to me that you have to be in the pre trial for finger tapping at NIH. it may increase your chances but everyone can't go alone and make it over to NIH off meds in tne morning once a month. That's grueling.so federoff, gill, encapsulated, and i thought federoff was medgenesis; could be wrong.they all still believe in it. now the latest is next spring in the usa.

About the Kinetics Trial at the NIH (the finger tapping trial):

I asked how many people were in the trial, I was told 12, and there are people on a waiting list to join it.

You have to go through this trial to join the GDNF trial at the NIH. I don't know if the NIH trial is Gill's method or not. Personally I would thrilled if this were the case.

Yes, in the NIH visits, you have to arrive for your appointment unmedicated (having taken your last dose of meds at least 12 hours before the appointment). But the NIH will send a caregiver with you for travel and to help you. So yes, it would be difficult (and very uncomfortable) for someone with advanced PD. With a caregiver to help you, it may not be easy, but it is possible.

You end up going to the NIH for 7 months in a row because the first visit & interview doesn't count as one of the clinical trial visits. It IS tiring when you live across the country and face a 4+ hour plane ride each way. The first visit I made, I flew in on Thursday, had the trial on Friday morning, and flew home Friday evening. That schedule was too hard on me, so they let me have 2 over nights for each visit now.

I may be mistaken, but I think LindaH and PerryC of this forum have completed the Kinetics clinical trial.

In other GDNF news:

Dr. Bankiewicz at Univ of San Francisco is working with: "convection-enhanced delivery of adeno-associated virus (AAV) vectors, and convection-enhanced delivery of AAV viral vector with AADC for the treatment of Parkinson's disease. " So is this possible future trial connected with any others? Gill's method is "Convection." Is this the same convection delivery system or a different convection delivery system?

I'm confused.

Jean

Yes, I completed the Kinetics study, which is testing devices for objectively evaluating movement. It might be used to provide outcome measures for the GDNF study. However I didn’t think that you have to take part in this study to be accepted for in the upcoming gdnf gene therapy study at the NIH . They did say the initial screening process would be the same, so if you were screened for the Kinetics study, you wouldn’t need to be screened again for the GDNF study. And participating in the Kinetics study also didn’t guarantee that you would be accepted for the GDNF study. The advantage might be that the clinical staff would know you and you would have 6 months of baseline data. Recruitment has not started (see Perry’s posting on the trial status.)

They do the device testing and a UPDRS evaluation off and on meds at each visit. I second Jean’s description of being tested off meds for 12 hours as difficult – even grueling. By my last appointment I was so off, I wasn’t able to do any testing until I took my meds. But the NIH staff will do what they can to help. They sent a taxi for us in the mornings , because I couldn’t navigate the shuttle bus to the NIH. Once you get there, there are wheelchairs available at the entrance. . They also offered to allow me to sleep at the NIH hospital the night before my appointment. And they ask that you attempt to do all the testing off meds, but if you can’t manage some of the tasks, then that’s how they record it. Having a care-giver with you definitely makes it more doable and the NIH will cover travel, hotel and food expenses for care-givers.

Linda, thanks for the clarification!

The staff did tell me you had to participate in the kinetics study in order to participate in a future GDNF study. But frankly what LInda says makes more sense. And yes - I was told that participating in Kinetics trial doesn't guarantee you a spot in the GDNF trial.

Jean

I was at the NIH clinic last week and the Neurologists as well as the RN had very little information about the upcoming GDNF gene therapy clinical trial. I am surprised to learn more about it here (Neurotalk) than at the NIH. also no mention of Kinetics device. I got info on DBS which I requested and about a couple of MRI-related trials. Why would they not publicize GDNF trial????????????

Girija

Robert D where are you and is your i phone app approved by the FDA? we need it now.
have you made one for the DROID yet? need that too!

sincerely,

Girija, I am as frustrated as you! I learned about the Kinetics trial and device here on Neurotalk. And when I asked about the GDNF trial at my last NIH visit, no one knew anything.

At one point I was told (by someone somewhere...) that they can't publicize a clinical trial that hasn't been approved yet. So I'm thinking that may be the issue. But it does everyone in the community a disservice to have such a lot of interest, but so little concrete information

Jean

(wonder status of this proposed trial. article dated June 2011. Interesting the delivery system is same as MedGenesis')

http://www.technologyreview.com/biomedicine/37708/
A molecule that has long been a source of hope as a potential Parkinson's disease therapy will get a new chance to show its benefit. A team led by Krystof Bankiewicz at the University of California, San Francisco, plans a clinical trial of an experimental gene therapy using glial-derived neurotrophic factor (GDNF), a protein that helps keep neurons alive. The team is in the final stages of gaining approval from the U.S. Food and Drug Administration, and hopes its trial can address issues that marred previous trials...


Bankiewicz believes that other attempts failed because they didn't target the right tissue precisely enough. The first attempts, he said, injected the GDNF protein into the spaces near the brain regions of interest, where it failed to diffuse far enough into the brain. Infusing the treatment directly into the relevant brain tissue, he says, caused leakage into the surrounding fluid...

The new trial will introduce the gene encoding GDNF into the putamen... The gene will be carried by a virus, and will be injected directly into the brain using a technique called convection-enhanced delivery, which uses positive pressure to drive fluid deep into targeted regions...



Once incorporated into cells, the gene would drive the expression of GDNF protein; Bankiewicz says it should then travel to other areas of the brain affected by disease, transported along axons, the long tails of neurons that connect brain regions.

... and scientists disagree over which factors need improvement: the vector that contains the genes, the delivery system, the targeting of relevant brain regions, the types of patients that are studied—or even the gene itself. Andrew Feigin, a neuroscientist at North Shore University Hospital, says that the recent setback in the neurturin trial casts doubt on whether a similar approach will work with GDNF...
Ronald Mandel, a neuroscientist at University of Florida, is also working on a GDNF gene therapy. He's optimistic that GDNF could help Parkinson's patients, but he believes it should be tested in patients at the early stages of the disease—before the dopamine-producing cells have become severely diseased and die off. Getting approval to test therapies in such patients, however, is very difficult.

Whoops, just re read entire thread and noted Jean posted about this trial. madelyn