iqbaliqbal has already posted about this. It is the single most interesting research to me, since taking an interest in PD. It's what I got seriously annoyed with John Pepper for slandering with false information, based on his ignorance. It's results are published in February, but I suspect not to the public until after these 2 TV programmes have screened.
They are guarding their secret. I may have called it wrong in stating the delivery mechanism worked but the drug was a disappointment. I wagged a finger (affectionately) at iqbaliqbal for repeating the programme title in his post. So, I'll wag a finger at me for doing it again
The Parkinsons Drug. A miracle cure? - BBC2 9PM UK time , thursday 28 February
I've read somewhere (can't remember where!), and heard from someone who works for one of the sponsoring organisations of the research that the outcome of the research is going to be made public on Wednesday. I may always be wrong
That would make sense. It's February -and just before the program. The hints, albeit in part from a broadcaster selling a program, are definitely positive.
Yup. I had posted those videos before. I get the feeling this documentary is going to have more positive conclusions than those early videos and to be bidding for funding for a further larger population trial. Possibly including mir7
Sorry, I must have missed your earlier post, but this one definitely has my attention. It seems unlikely that the BBC would devote a series of shows to a failed trial. I think we have reason to be optimistic. Thanks for sharing this!
Perhaps they could try ocular administration (eye drops) of GDNF (or a GDNF inducer); I don't know if it would get into the appropriate brain region (substansia nigra) at the appropriate amount, but it seems at least worth trying in an animal model. Ocular administration of NGF appears to get to various brain regions in rats:
I think not. If you watch the program you will see part of the challenge is getting gdnf where it's needed and ocular administration would not be sufficiently targeted.
I just get a 2-min preview; it says the program will be available after broadcast.
If NGF, a 130 kDa three protein complex can get all the way to the rat hypothalamus via eye drops, then I don't see why one would discount even the possibility of GDNF, at ~30 kDa (as a homo-dimer), getting into the substansia nigra. Seems worth a try (in animal models), anyway.
Eye drops are not complicated to use and do not require medical hands on procedure. I imagine the cost will also be a fraction of GDNF infusion to the brain.
It would have to be tested - one cannot say if it works or not without running the appropriate experiments. If a much larger neurohormone, NGF, can get into deep brain regions via eye drops (no ultrasound was used), then why not GDNF? There is no way to know without running experiments. Perhaps it has already been tried and a negative result was found but not reported in the literature. The lack of reporting of negative results is a known flaw in the system of scientific communication. Or perhaps a negative result was published and I have not turned it up in any of my literature searches. Please advise if you know this to be the case.
~
Do well-trained scientists sometimes overlook things? It happens. After completing an MSc in an unrelated field (marine biology) I interviewed for an immunology PhD program at a well-known university. During a one-on-one session, a professor told me about a knockout mouse he had created; this was before CRISPR and creating a knockout was a big deal. The gene in question was, of course, related to immune function. He went to a conference and found that other scientists were working on the human homolog; they had found that a mutation in the gene results in a form of congenital blindness. After relating this, the scientist asked me, "I went back to the lab, and do you know what I found?" I did not answer since I was dumbfounded as I realized that apparently there was no standard battery of phenotypic assessments done on new mouse lines. He had not known his mice were blind.
~
Here's another article on ocular NGF; unfortunately it is also paywalled, but from the abstract if appears oNGF found its way to the cerebellum and reduced inflammation:
I was too hasty - I apologise. You make your point well with your subsequent post. Clearly FUS IN has yet to be trialled in humans, and there are many variables, but at least in principle , if developed it might offer a better delivery mechanism. Thank you
Sorry, but in my humble opinion, this Parkinson's treatment that requires brain surgery falls short of a "miracle cure":
It looks like they are targeting the substantia nigra. It is true that this is the area most affected by Parkinson's, but this will not be a complete cure because other regions of the brain, and for that matter other parts the body, are also affected by accumulations of faulty alpha synuclein. This underlying problem is what must be addressed to affect an actual cure.
So this will be yet another remedial treatment requiring brain surgery for those with advanced Parkinson's. That is okay, it is a good thing, but as to "miracle" - nope.
I think the approach by Denali Pharma, currently recruiting for phase 1B trial is a lot more promising. Although it is specifically targeted at the LRRK2 gene mutation, it is possible it may work for Parkinson's in general, and it does target the actual cause - failure to properly recycle used alpha synuclein: healthunlocked.com/parkinso...
I am trialling a monoclonal alpha synuclein antibody right now. Gdnf is different in that,if I understand correctly,it can repair the damage and reverse the disease. Might be worth watching. Some of the results look significant. But I agree, the delivery mechanism is elaborate and expensive
As PDC and I discussed a cure for PD involves 3 elements. A disease modifying element to slow or stop progress (maybe an alpha synuclein antibody) a neuroprotective mechanism and a repair of the damage to restore dead neurons. For the repair stem cells, also involving brain surgery are the headline grabber but gdnf infusion has some better qualities
IMHO, if something is dead cannot be brought back to life. Unless, as Dr. Berger claims (and I believe to be true), neuros do not die, they hibernate, they are inactive, like snakes in the winter time which come alive in the spring/summer time.
Clearly we should reserve judgement until it's aired, but the clip seemed to state it works for some but not others (not including the placebo group I assume) so same as every other treatment then!!! and I don't think our bbc are immune from 'not letting the truth get in the way of a good story'.
Thanks. It remains one of the most interesting prospects for restoring function to PWP as part of the combined cure of slowing disease progress, protecting neurons, and reversing damage (especially if the mir7 research proves helpful). The PETscan evidence of improvement is particularly encouraging. As Park Bear pointed out, many aspects of PD may not be due to dopamine deficiency in the SN and it appears a weakness of PD research interpretation to consider a treatment even a partial failure if it only treats some aspects - ie not all symptoms improve. I am looking forward to tomorrow nights programme.
Yes John Pepper stressed GDNF but with little or no understanding of what it is. On this forum, in spite of being corrected by me, he persisted in repeating that the GDNF in this trial (the one in the TV program) was "toxic in the brain", because it was "artificial, since natural GDNF couldn't be toxic". So doubtless the research group ( who do understand the subject) were thrilled by his ignorant bigotted contribution. He was wrong - but showed no shame in persisting with the false and misleading claims, and no interest in understanding the subject, and made no attempt to offer any evidence for the complete garbage he was posting. He frequently and repeatedly demonstrates his lack of understanding of the subject. Hearing about something called GDNF and deciding it is the reason for his recovery due to its production by his specific exercise regime, and expressing hostility to research of this kind is not the same as understanding the subject. It is JP's private fantasy - made public. He heard a word, and uses it to bolster his credibility. He fails to understand what it is, and believes science is running a conspiracy to keep us from this miracle out of spite. And deliberately and knowingly and inaccurately persisted in slandering this research.
These TV programs should help demonstrate to him, and anyone wishing to believe his nonsense, that he was wrong, that the GDNF was not "toxic in the brain" , and that nobody is going to measure JP's or anyone elses GDNF in the brain resulting from exercise, cos its a bit trickier than that.
I should probably clarify I have no hostility to John Pepper as a person. I admire his positive attitude to a chronic health problem , and his determination in resolving it. I have become aware of some background to issues others have with him, notably the fact that his own description of his diagnosis, makes it more than possible that his chronic illness was not Parkinsons disease, but that has not been any concern of mine. I have 3 specific issues with JP
1) posting excessive length posts about JP in the middle of other peoples threads about other subjects. This started with a complete biography being dumped in the middle of a thread about an Australian research project into a new "miracle drug". I reported this and site admin removed the post. I explained to John about the basic good manners of not ruining other peoples threads that way, and I have to say, he seems to have taken the point. If he has been trashing other peoples threads, they havent been ones I have been reading. So we can be friends on that point. (I realise this is long and not directly relevant to the subject of the post - but it is MY thread I am abusing! Not someone elses)
2) Posting factually erroneous defamatory information about the GDNF research in this trial at Bristol which is the subject of this BBC documentary. No need to labour the point made in my other reply. He was wrong, and persisted in repeating the rubbish without offering any objective support for his claims, or showing any understanding of explanations given to him
3) He routinely denigrates research such as this as a waste of time, as for him, the only way of reversing Parkinsons Disease is to do what JP says. He compounds this in a self-pitying fashion, by effectively accusing the scientific community of deliberately avoiding discovering a cure, or useful therapy for PD, as a way to make money out of making JP personally suffer. Mercifully the scientific community ignores him, and gets on with tackling the tricky subject of improving PD for people like me. I am resolved to take a stand on this whenever it comes up. Not just by posts on forums, but by participating in that research. I am currently on a trial for BIIB054. I very much hope that will help millions of PWP to benefit from a new treatment. At the very least, it will help advance understanding and contribute to an eventual solution. Telling people pharma companies are just in a conspiracy to make you suffer I feel is somewhat less helpful.
OK, you have discredited JP, would you discredit a Mayo neurologist who suggested to my husband that only INTENSE exercise can slow the progression of PD. Wonder why he recommended that?
How much does this therapy will cost a PWP? How much does fast walking cost?
How many high tech companies and their personnel are involved? How many doctors are required for the procedure and never ending follow ups? What about people who can't afford it, or will social medicine pay for this therapy? There is no social medicine in the US and insurance will not pay until approved by FDA.
Yes, it is all about money/profit! Only when there is actually a cure or reversal of PD, only then I will believe in all these "miraculous" results of clinical trials. Until then, we will continue our fast walking or any other form of intense exercise and our HDT therapy.
PS. Did you ever work so hard that at one point you couldn't go on, having a brain fog, took a long break, went to the gym to do intense aerobics, or went for jogging and at the end of this routine, after showering, you felt so refreshed and clear minded? What caused this refreshing/relaxing feeling?
There is widespread advocacy for vigorous exercise in PD. It's not unique to JP. I take it you are one of the fortunate ones who has no need for medication and no cause for gratitude to the scientists and business which make it available. I continue to support efforts to improve life for PWP.
Not me, my husband was diagnosed March 2018 by Mayo. No meds yet, just MP, vitamins, amino acids and HDT. Like I wrote, until I see REAL RESULTS from clinical trials, let me have my reservations. . .
You should be aware MP is "meds". A levadopa supplement masking your husbands symptoms. Ignoring JPs advice to avoid levadopa and use maob inhibitors.
I am also one year since diagnosis. And I am truly not on meds. No sinemet. No MP. And like your hubby doing Ok. Don't count on that 1 year experience telling you anything about how we'll be 10 years from now.
Among the frustrations is the fact that people improved on the treatment. But also improved on the placebo. It's not that the drug didn't work,but that it wasn't a big enough and long enough trial to prove it worked
I've tried to stay up on this. Is the stuff Zhittya is trying to get to trial, or similar? Seems they are very positive that lack of adequate blood flow to the brain is a setup for PD, ALS, LB dementia, even MS. In the meantime keep moving. Tc and God bless. Too many brilliant, dedicated and compassionate minds are on this. Stay in the game PWP, we are so close.
If you go to the bbc program website and from there look at the actual extension study research article, which is free and open, the results there are pretty clear.
Or you can just read the study at the journal article websites. There were two, and I read through this one:
They commented on disease progression, which I was less interested in in my quick read-through, and the clinical outcomes (practical effects the patient experiences), which I did read closely. So if you want to see if the disease progressed or was slowed, read it yourself, not that very hard if you go over it a few times.
In practical patient experiences, the stuff did not work over the 80 weeks, by which I mean no meaningful difference from placebo.
They go on to state that since the control arm of the study has now been lost, to further study would require either a new study with proper controls (double blind) and 80 weeks to do, or use a higher dose.
Well - lets hope the BBC make good programs. As I commented on my original post when iqbaliqbal drew our attention to this program, headed "Spoiler alert", I was fairly sure the results were disappointing. I am not sure how much this reflects the limitations of our evaluation techniques. I am pretty sure you will see people on the program experiencing better life as a result of the infusions. And being disappointed that the trial result does not support their continuation of those benefits.
My interest in this topic, is that GDNF potentially restores neurons. A cure for PD is never going to be as simple as a quick pill which stops it developing and restores a pwp to a fully normal brain. It is going to require AT LEAST 3 elements. A disease modifier, a neuron protector, and restoration of existing damaged cells. The first 2 may have multiple causes and solutions, possibly in combination.
For example, ParkBear drew attention to alpha synuclein. I am participating in a trial to block the aggregation and spread of this protein using a monoclonal alpha synuclein antibody, so its not like I am disinterested in this field. But whilst there are a lot of smoking guns, there is no proof that a-syn is a cause of PD. Never mind THE cause of PD. glp1 receptor agonists, calcium channel blockers, iron chelators, and anti-inflamatory options are all possibilities. Probably PD is not one thing, but a group of consequences from a group of causes. But we can group all of those as "disease" and potential treatments for them as "disease modifiers".
Let's dumb it down. The disease is due to A-syn, and my BIIB054 antibody is going to clear the A-syn and stop the disease. My avatar shows you my Datscan. 80% of my neurons in the SN aren't functioning (based on post mortems of others, are dead). Stopping the disease process, stopping more of them dieing, stopping some of the other shit that A-syn may be causing directly, rather than as a result of dopamine loss (like constipation), isn't going to give me 70%, 60% , 50% or better neurons.
(NB - if we can detect PD earlier, and stop the disease, then the neuron replacement element will be redundant for future generations. However, right now, there are millions of people for whom it is essential for a complete cure. Until then, dopamine supplementation - Sinemet - is the partial solution for this aspect)
That 3rd part of the deal - replacing neurons that have been lost, is a separate issue. The main focus, most of the posts I have read about it on this forum, are based on stem cell replacements. That too is a source of great hope. But has some issues. It also requires brain surgery and is expensive. It has had some spectacular failed clinical trials in the past (with earlier versions). Current trials are of small size and will suffer the structural weaknesses of this GDNF trial. And although the cells are in situ, and produce dopamine, they are not integrated into the brain in the way the lost cells were, and so there are still issues with diskonesia and the like from a potential oversupply of dopamine.
GDNF is another potential solution to this 3rd aspect of the cure . (It has the benefit that it is potentially also an answer to the neuroprotective bit)
(a very simplified short version)
In mice ( I know, I know, PWP are NOT mice) - in mice who DON'T have PD, but have their brains chemically damaged to have the damage PD causes, and so behave like they have PD - GDNF grows new neurons with good connections and restores normal behaviour to the mice.
It sort of works, but doesn't work well enough in people. Well - maybe it just doesn't work in PWP. If we took some normal healthy people and chemically damaged their brains the way we do the mice, maybe it would work. This avenue of research is of course closed
Further research at Bristol suggests that maybe the GDNF doesn't work so well in PWP is due to, our old friend, alpha synuclein. (It may also be , in the context of the trials, because the experiment has been not enough drug for not enough time. New neurons take time to grow and make connections)
PWP have excessive A-syn in the neurons (not misfolded , or aggregated A-syn, regular protein) and this binds to GDNF and stops the GDNF binding with the growth receptors in the cell. This seems to be due to the lack of a short "micro-rna" strand produced in healthy cells, but deficient in PWP - known as mir7. Mice with chemically damaged brains have no lack of mir7 in their cells, like real PWP do. mir7 binds to A-syn, and so stops the A-syn binding to GDNF, and so leaves the GDNF free to do its growth stuff in the cell.
So Bristol are looking at a combined GDNF and mir7 therapy called GDNF7. At the moment, that testing is at the mouse stage
A very long winded way of saying that the "failure" of this trial, in terms of the clinical testing objectives, may not be the end of a fascinating and promising line of complex research
I am hoping the program, when I see it tonight, and part 2 next week, may reflect that.
(But in my very first post, to iqbaliqbal's post, I pointed out that the program title might be a bit misleading)
Thanks. I'll read more after watching the program, but the summary I read did a much better job than my previous ramble, so I'll "borrow" it
Short summary if you’re in hurry
· The GDNF clinical trial tested an experimental new treatment that was infused directly into the brain using pioneering surgery and a purpose-built delivery system.
· Early results after the first 9 months failed to show a difference between the GDNF treatment and placebo. However, these initial results only scratched the surface of what was really going on.
· Full analysis of the data shows that GDNF was more successfully delivered than in previous trials and appears to help dopamine-producing cells to regrow.
· Over the course of the trial, the 41 participants experienced substantial improvements in their symptoms and everyday lives.
· The full results highlight that GDNF may yet offer hope to reawaken and restore the brain cells that are gradually destroyed in the condition. To make this a reality, we’re working with partners to push for future trials of GDNF.
I have no direct experience of mannitol. If you are asking about whether consuming mannitol mends PD by supplying gdnf in the bloodstream generally or in the brain specifically this trial shows it ain't that simple
No, not as a cure. I read your posts, and realize I'll never have your depth of understanding.. I just figured you were probably familiar with it, or the Israeli study...basically just wanted your impressions.
I know someone who was in the trial. It was really helpful but she got an infection in her brain and they had to take the port out. Seems like a very invasive treatment. Also as Big Pharma aren’t involved in the trial it’s unlikely it’ll ever be available as a treatment.
Interesting that you know someone in the trial. Yes it is a very invasive treatment - as is its main "competitor" - stem cell transplants
Big Pharma aren't involved - but again, neither in stem cell transplants. Whether it is ever available as a treatment will depend on whether it can ever be refined to the point it demonstrates efficacy, and will depend on pure research funding.
There are several other costly treatments for which Big Pharma have no opportunity like deep brain stimulation and MRI treatment.
Maybe the publicity from the BBC2 program will help with fund raising.
Thank you for all the information you have provided… I am very interested. I want to view the BBC programs, but I am in the US, and apparently I will need a TV license to view the programs (expensive). Do you know if there is any way around this or if it will be likely that someone will post the programs to YouTube for later viewing? Thank you again
As I posted earlier get a vpn, pick a UK server and go to BBC iPlayer. Maybe it will be on YouTube too. I am in France and have to use a vpn and iPlayer to watch it
Thanks, I do have a UK VPN, and I have iPlayer, but I understand you still need a TV license to be able to watch it, which is 150 Pounds, so appears those outside the UK will need to hope it is uploaded to YouTube to watch it.
You are supposed to have a TV licence to view any TV program from any point in the UK. However iPlayer is not going to know. Even if you have a TV licence you are not supposed to watch UK TV broadcast outside the UK. It is very unlikely that the BBC will upload to YouTube so any stream there would breach copyright.
I thought the first episode was good. Informative and interesting. Looking forward to the second episode. Awesome respect for the participants. Also I think it shows that most people in research are there to help people and not for the money
I’m keenly interested in the summary points as gaining access from USA is cumbersome and frankly, summary by a capable viewer would be more valuable - and precious!
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what's your experience with azilect? 
Azilect
MyLovedHadPD
Will Tasigna, an FDA-approved cancer drug, be the first drug to revere symptoms of Parkinson's and dementia? 
