“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."
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 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(?). 🤔
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?
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?
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.
"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.
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?
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.
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....
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.
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.
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):
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.
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.
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"
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?
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 .
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.
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?
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."
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:
“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:
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