Neurotrophic Factors Update: "Improve... - Parkinson's Movement

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Neurotrophic Factors Update: "Improvement of 100%"

PDConscience
PDConscience

“I believe that this approach could be the first neuro-restorative treatment for people living with Parkinson's." - Steven Gill, MB, MS, FRC

"Researchers used robot-assisted neurosurgery to implant a specially designed delivery system, termed Convection Enhanced Delivery (CED), which allowed high flow rate infusion to be administered to patients every 4 weeks. Patients underwent a procedure to have 4 tubes implanted within their brains. GDNF was directly infused to targeted locations via a skull-mounted transcutaneous port located behind the ear."

"Positron emission tomography (PET) brain scans from the group who received GDNF showed an improvement of 100% in the targeted area of the brain affected by Parkinson disease, leading researchers to believe that the treatment may have the potential to reawaken or restore damaged brain cells."

Full Article: ajmc.com/newsroom/new-treat...

60 Replies
oldestnewest

Hi PDConscience, I kind of remember having read that it finally did not work on PD and this paper only says the system was well tolerated by the patients - should I say the heroes - of this trial.

I definitely hope I'm wrong on that one.

PDConscience
PDConscience in reply to Xenos

I suspect your memory is accurate, Xenos. You probably got your hands on a more objective report on the studies' outcomes. When read closely, this version is ambiguous (or misleading?) at best. One paragraph begins by boasting, “Positron emission tomography (PET) brain scans from the group who received GDNF showed an improvement of 100% in the targeted area of the brain affected by Parkinson disease, leading researchers to believe that the treatment may have the potential to reawaken or restore damaged brain cells" - then concludes with, "After the trial period, no improvements in symptoms were observed in either group."

Since "improvements in symptoms" are the primary concern for most of us, study outcomes that offer none become a bit tedious.

Maybe researchers will eventually be able to use that 'Convection Enhanced Delivery (CED)' BBB-busting contraption to deliver something that actually works(?). 🤔

I know people who were in the trial. GNDF definitely works!

Xenos
Xenos in reply to Trixiedee

Could you give more details ?

Trixiedee
Trixiedee in reply to Xenos

Well it definitely reversed symptoms while on the trial, all the participants were heartbroken when Pfizer pulled out. Have you seen the BBC series?

youtu.be/PN5bJ-ookJk

Read a Feb 2019 update on GDNF research at

medium.com/parkinsons-uk/gd...

Why would anybody want to have a very expensive and risky operation performed on their brain when the brain produces the GDNF naturally? We should be spending our money on finding ways to produce MORE GDNF NATURALLY! Why are we not doing it?

jeeves19
jeeves19 in reply to JohnPepper

For the simple reason that exercise doesn’t produce enough GDNF!

This simple fact has been pointed out to JP on NUMEROUS occasions. He’s not wired to process such pesky details.

JohnPepper
JohnPepper in reply to jeeves19

That's peculiar! It has done do for me and it is doing so for many others I know.

LindaP50
LindaP50 in reply to JohnPepper

I totally agree with you John. Very invasive and risky.

I will testify! I had my back surgery 2 weeks ago , now I can walk again. Im up to 2 miles a day and my symptoms are improving across the board.

Well done!! Thanks for letting everybody know! Keep up the good work but DON'T OVERDO IT!

Im going for my third mile today right now . All the while, listening to Joe Dispenzas book, You Are The Placebo, on my kindle audio book.

So glad to hear it bass. Glen is still suffering terrible pain, mostly in his calves. The nerve block injection he had last month didn't work. It made the pain worse if anything. 🙁

What type of surgery did you have & what's the name of the procedure please?

Thanks

Gerry

I had a laminectomy and facetectomy of lumbar 2-3, 3-4, with fusion including instrumentation (rods and screws) and endogenous and exogenous bone grafts (autograft and allograft) . If you get a consultation with a neurosurgeon, they'll get an mri and they'll know what to do .

It was a huge 4 1/2 hour sugery but they did a heck of a great job! Plus im a great healer and i attribute much of that to whey protein isolate smoothies every day, and clean living!

When I had my first laminectomy my neurosurgeon warned me NEVER have a FUSION because the vertebrae are meant to move and if they can't move the tend to cause problems at both ends. I had a second laminectomy in 1998 to the one above the first one, and again I had no fusion. I have skied and done all my fast walking since 1994 and have had no further back problems. Everybody I know who has had fusions have all had problems. My wife had a fusion after her laminectomy and she has had nhting but pain ever since. They cannot reverse the fusion so she just has to live with it.

You cant say never. There are certainly cases where fusion is appropriate and necessary. In my particular case, we did xrays with me bending foreword and backwards. These showed instabilities and shifting, which would be even worse once the lamina are removed. Yes, i do feel slightly more limited in my range of motion, but its a no brainer of a trade off for the painless life got in return. Believe me, this dr did not want to just fuse me wiilly nilly. We went into it very carefully!

I only passed on what the specialist told me. I cannot speak for anybody else. I agree that no two people are alike and circumstances will always dictate actions.

one of the participant's comments:

"I was on the trial and I thought that there was a difference but not statistically enough of a difference to be deemed to have reached the endpoint. Could you check this out as failed to show a difference implies it did not work at all as opposed to failed to show a significant difference, which implies some success. As it was we all found that the GDNF infusions helped our symptoms and the dopamine producing cells certainly regrew.

Many thanks,

Julia"

youtu.be/gnDHMveS9_M

😊

Impressive. Leaves one to wonder about the duration of any improvement of symptoms - lasting or temporary? Can the patient eventually shed the convection apparatus, or must they remain cyborg (requiring regular infusions) for life?

Hikoi
Hikoi in reply to PDConscience

This is one of the original 6

PD. You missed a really good documentary here in UK by the BBC filmed over 5 years. There was a discussion on this site about a month ago. Sadly the BBC seemed to have taken it off YouTube. This is unhelpful as the world needs to see the opportunity that Pfizer have abandoned. The treatment worked for so many of the volunteers although it took varying degrees of time. The results published that it didn’t work were utter nonsense and based in the erroneous method that sadly formal science tends to get carried away with. The volunteers had a monthly infusion and in many the effects were impressive and long lasting.

JANVAN
JANVAN in reply to jeeves19

Exactly jeeves !!

I am searching all over the internet to get the second part. We are old and smart enough to “filtrate” the results. Who aren’t totally positive, but also not totally negative.

But really strange that this disappears after, I think only three days online.....

That is then also moredifficult to persuade investors for the continuing of the trial (which Prof. Gill certainly want to do !). Good Ian Franzell has also post a video (here on the forum), concerning the best way to spend....

jeeves19
jeeves19 in reply to JANVAN

Sadly the BBC has a bit of a thing about wider publication of its programmes. They remind me of Prince! Need to loosen up a bit I think😬

youtu.be/u7zwRNyRz24

This is available however

I'm guessing this was the first trial with 6 subjects. I'm encouraged by the positive outcomes, but discouraged by the failures (also sorry about Tom Isaacs' passing). Let's hope they get the kinks worked out.

Hikoi
Hikoi in reply to PDConscience

42 participants I think. Did it work? Read this.....

jonstamford.com/2019/03/17/...

PDConscience
PDConscience in reply to Hikoi

Interesting - Stamford provides an objective, more informative analysis of the trials' outcomes. As he points out, researchers have different criteria by which to determine a trial's worthiness. As a patient, tangible relief of symptoms (as typically measured by UPDRS) is primary. From every angle, however, GDNF therapies for PD appear worthy of further study.

Xenos
Xenos in reply to jeeves19

Remarkable Jeeves. This is a must-see.

faridaro
faridaro in reply to jeeves19

I could hardly breathe watching this clip - what a courageous group of people, hope their improvements will last.

jeeves19
jeeves19 in reply to faridaro

Sadly they won’t. They need their monthly infusion and this has now stopped. What a shame eh?

faridaro
faridaro in reply to jeeves19

Horrible, simply inhumane...

It seems that although the PET scans indicated a strong response to treatment, the effects upon the actual signs and symptoms of illness were not different from placebo. This is very intriguing but not at the moment directly helpful. Here's a great rundown of the results aimed more at a non-researcher (although still very technical):

scienceofparkinsons.com/201...

And here is the (more technical) article describing the results of the study:

academic.oup.com/brain/arti...

Slightly earlier version:

content.iospress.com/downlo...

Hikoi
Hikoi in reply to LouThomas

An analysis of the results is given here.

jonstamford.com/2019/03/17/...

LindaP50
LindaP50 in reply to LouThomas

I watched most of the video and made me very sad to know something worked and then the plug was pulled.

Hikoi
Hikoi in reply to LindaP50

Yes and invasive and risky, do you think people would have agreed to this if fast walking worked? There is no proof I have seen that exercise produces GDNF, it may produce a growth factor but i cant find the evidence.

danfitz
danfitz in reply to Hikoi

Here is one link. There are others:

alterg.com/treadmill-traini...

danfitz
danfitz in reply to danfitz

ncbi.nlm.nih.gov/pmc/articl...

Hikoi
Hikoi in reply to danfitz

Thanks danfitz

First i will repeat that I am not against exercise and I believe it does benefit pwp, I have seen it myself.

I think we dont fully understand how and why so making claims that it is due to GDNF may be true but it may be BDNF or another factor. Of the three studies on your link one refers to GDNF and it and one other are with animal models which may or may not be the same as in humans. The Bristol experiment showed to me that placing GDNF in the brain reversed the decline but that is not to say exercise produces GDNF. That is thought to happen but it is not proven and in fact does not work (in rhodent brains) if there are high levels of alpha synuclein, such as is found in the brains of pwp.

GDNF Protein: 50+ Ways to Increase It + 14 Benefits ... Self-Hacked 4/1/19

selfhacked.com/blog/gdnf/

faridaro
faridaro in reply to MBAnderson

Good information and interesting comment: "the ability of GDNF to improve symptoms of Parkinson’s disease in rodents depends on the disease model used. For example, GDNF is not able to help in models where alpha–synuclein is overproduced"

MBAnderson
MBAnderson in reply to faridaro

I saw that and wonder if it might be in conflict with some of the experiences of the trial.

faridaro
faridaro in reply to MBAnderson

Good point!

Wonder if ultrasound wouldn’t do the same thing Without having to actually put something structurally inside the skull. Using the ultrasound on a lower setting?

Hikoi
Hikoi in reply to Sandmanliz

How would ultrasound deliver a drug every month?

JANVAN
JANVAN in reply to Hikoi

<<<

Hi, perhaps like this ........see the link of PDConscience about that Prof. of Columbia University, Elisa Konofagou !

This is quite a good description of what happened.

medium.com/parkinsons-uk/gd...

Thanks for sharing this very informative link. Hopeful.

It is my understanding that gdnf nourishes the cells of the brain and restores function. Therefore I think it makes sense that when treatment is stopped, the cells atrophied because the underlying cause has not been addressed. Or it could be placebo effect , which has been demonstrated to be extremely powerful in Parkinson's disease .

Hikoi
Hikoi in reply to bassofspades

It is more than placebo as the Bristol trial proved.

To me this is more tragic evidence of how capitalism does offer incentives to drug companies to look for real answers. First off the principle of a single bullet treatment for a complex neurological disorder like Parkinson's is flawed in itself. Next, if GDNF is the magic bullet that can help why experiment with a highly complex and incredibly expensive delivery system without first exploring nasal mists or eye drops or nano-particle designs first. These would cost pennies per day as compared to needles placed in the brain.

Really just tragic . . .

Hikoi
Hikoi in reply to sunvox

Wouldnt nasal spray or eyedrops face the problem of the blood brain barrier? Dont know anything about using nano particles, how would they be delivered?

sunvox
sunvox in reply to Hikoi

No. There is tons of research on getting chemicals to the brain via the nose and the eye. In fact it is used in some treatments today. In one famous case a woman Nobel scientist gave herself Nerve Growth Factor eye drops every day and lived to be over 100:

"Levi-Montalcini was awarded the Nobel Prize in 1986, and to this day, she uses eye drops — eye drops containing NGF. And now, she’s almost 103 years old. Apparently, the NGF that Levi-Montalcini helped to discover directly affect the survival of neurons and brain function. And it might be a very effective way to treat or prevent diseases such as Alzheimer’s or Parkinsons."

themarysue.com/rita-levi-mo...

Obviously different molecules have different levels of permeability, but think of the most famous drug that gets to the brain by inhalation, namely nicotine. Take a puff of a cigarette and nicotine hits your brain in seconds, and actually the eye can be an even faster route.

Nano-particles are why I take Theracurmin and not other types of curcumin supplements:

sciencedirect.com/science/a...

ncbi.nlm.nih.gov/pmc/articl...

data.integrativepro.com/pro...

Hikoi
Hikoi in reply to sunvox

Thanks, interesting. I believe that we take levadopa because dopamine will not pass through the bbb. Is that correct?

Hikoi
Hikoi in reply to sunvox

ncbi.nlm.nih.gov/pmc/articl...

“The results of these studies are consistent with the following conclusions. First, GDNF does not cross the primate BBB.

In summary, the present studies show that re-engineering GDNF as an IgG fusion protein can enable brain penetration of the neurotrophin following intravenous administration in parallel with a decrease in GDNF uptake by liver, spleen, and kidney. The brain uptake of the HIR MAb-GDNF fusion protein is sufficient to produce a pharmacologically significant increase in cerebral GDNF.”

Perhaps the later method was still experimental having been tried on monkeys but not humans.

Now there is an additional study that delivered the GDNF via an AAV viral vector instead of through surgical tubing. The virus itself is delivered through a minimally invasive, one-time-only surgical technique (convection-enhanced delivery).

This study was not placebo controlled, and was quite small, but over the course of the study there was no decline in function as indicated by UPDRS, whereas some decline would have been expected. The full study report has yet to be published, but an abstract is available here:

aans.org/Annual-Scientific-...

Here is an account of the study:

scienceofparkinsons.com/201...

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