GDNF trial results

[Hikoi]

GDNF trials have been underway in Bristol for a number of years. Preliminary results .

parkinsons.org.uk/news/7-ju...

[soup]

I hope they find something hidden in the data!

I want to say a thank you to all those people who undertook the surgery, regular visits to Bristol for infusions and assessments, and were able to do all of that for the two years of the trial.

Negative results are still proof of something. Without volunteer participants we would have had no results, not negative results to help researcher understand the system.

[laglag in reply to soup]

I agree. Thanks to all participants!

[BillDavid in reply to soup]

Looked at the article you referenced. talked about one phase of a two phase study by Bristol.. The total subjects are indicated to be 41, a small number to use to project general outcomes. It talks about administrating both the GDNF and a placebo. How is it administered? One of the replies mention that surgery is involved? GDNF research goes back to animal studies (University off Pittsburgh?) The take was that the effect eas associated with high intensity exercise. This is presented in the Frontline Video by Dave

Iverson, My Father, My Brother and Me. Should be able to find in PBS archieve. Next came the bike studies from the Cleveland Clinic (look on you tube.. An effect of symppom remission was found at the intensity for pedaling at 90 or more cycle.s. Has been reported by others to be applied to other forms of exercise. PwP have written this up in books etc. Not aware of major academic study. Sense the generation of GDNFF is thought to be endogenous, the effect is measured in terms of impact on symptoms.

Regards bike pedaling,,. Swedish Resarchers are reported to have an experiment where only the right leg of the subject is exercised.

An effect of 5,ooo more methylaions where observed. These are thought to be associated with epigenetis., which in turn could explain the GDNF effect?

BillDavid .

[JohnPepper]

Hi Hikoi. How is the GDNF put into the brain?

John

[soup in reply to JohnPepper]

Did you read the exerpt John? Does it say in there?

[JohnPepper in reply to soup]

Hi Soup. Yes I read it but it was in Medical language and simple people like me don't understand it.

John

[soup in reply to JohnPepper]

John, if you'd like to list the medical words you didn't understand I will try to help you with them.

[JohnPepper in reply to soup]

Hi Soup. Here it is: delivered via intermittent bilateral intraputamenal infusions using convection enhanced delivery (CED). Can you make out a catheter inserted into the brain from that?

John

[soup in reply to JohnPepper]

Well, the phrase you used wasn't in the article. In fact, the delivery system wasn't mentioned as far as I can see.

Are you happy with my translation of what you wrote?

I'm not sure how convection enhancement works, but the rest means that it was delivered, now and then, into the putamen region on both sides of the brain.

Where did you phrase come from? I will go to the source and try to help.

[Dap1948 in reply to JohnPepper]

In the Bristol experiment the GDNF was inserted through a catheter inserted into the brain. You met Paul in Bristol who was a volunteer in the research

[JohnPepper in reply to Dap1948]

Hi Dap. That was back in 1993. I gathered that this trial was a lot more recent. I just can't imagine that patients would willingly allow a hole to be drilled into their head and have a ctheter inserted for the rest of their lives with the off-chance that they would get a genuine GDNF infusion and not some benign substance with unknown results. Now they have to walk around with this catheter in their brain for the rest of their life. Do you know if Paul is still receiveing these infusions of GDNF after 23 years?

GDNF is a natural substance which is produced in the substantia nigra, where it is needed and all the patient has to do is some healthy exercise.

Thanks for your input Daphne, it is most appreciated

John

[soup]

Infusion through a portal into the brain.

[WinnieThePoo]

Having discussed this on another thread with JP I had wondered whether to start a new thread about the research I referred him to. The following links should help explain the research, GDNF itself, and why I am interested in participating in a trial of a drug which inhibits alpha synuclein (A-syn). (And poo management - a lot of the A-syn overproduction is associated with the gut-brain axis and the vagus nerve)

As John will see (should have seen by now) the patients did have a novel , sophisticated , permanent catheter arrangement fitted, allowing GDNF or anything researchers want to trial, to be delivered precisely to the correct part of the brain.

Translation for John

intermittent bilateral intraputamenal infusions

intermittent (not constant - I think monthly)

bilateral (applied to both sides)

intraputamenal (within the putamen - a part of the substanti nigra region of the brain where PD destroys dopaminergic neurons - the tail on the comma in my DATscan (virtually no visible putamen on my right side))

infusion - drip application of the drug in solution

The trial was a success in terms of the long term viability of the delivery mechanism, but disappointing in terms of the dopamine neuron healing. The current theory is that this was due to inhibition of GDNF uptake in the cells due to overexpression of A-syn. This is due to the absence (or serious defecit) of an A-syn regulating microRNA in PWP (mir-7).

The GDNF used in this an earlier trials exhibited no toxicity - contrary to claims made by JP

Original trial

youtube.com/watch?v=XcZQEct...(Not working as expected?)

youtube.com/watch?time_cont...

GDNF-7 trial

youtube.com/watch?time_cont...

[WinnieThePoo]

I see I failed again with my links. For anyone interested in the other 2 links they appear to be working on my "Explaining to John Pepper" thread. Bloody technology!