I am stuck about this. I was always very willing to fund PD research. I saw it as the only way to cure parkinson's disease one day. I am monthly sending money to the MJFF foundation. 100 US Dollar a month. However, I am not sure anymore if I want to keep funding the PD research community anymore. I am thinking of stopping my funding. I know I am annoying about it; but the whole GM1 gangioside story has put myself thinking. I expect a certain commitment from a community if I fund. People funding all PD organizations, do so because they want a cure to be found. And if a cure (or something that is very close to a cure) is available, funders want to see the community to push for it. And if they don't push for it, funders want to know a valid reason for it; a valid justification.

I don't see this happening. To me it looks more like a game where money of funders is used to play games. You know, these typical games that are played in research. I mean, like playing with people's hard earned money. In a way like "Let's play with some fruit flies and mice and let's test this new compound on them. Ohh, wouw, look, the fruit fly can fly 2% better than before. Awesome. Now let's publish a paper about it in a high impact journal. OK, paper published. Let's throw the results in the garbage and let's start some new compound testing on fruit flies again. This is the fastest way to publish a new paper." ... I may sound nuts when I say this, but I have been in research and I know how research goes and what drives research. And the whole GM1 Ganglioside thing, reminds me of it. And in this case I guess there are even other factors that play a role. Like the companies selling drugs for symptomatic relief. They are not interested at all in a compound that can be seen as a cure. so they might do their best to slow down the development of these new drugs ... untill their patents expire.

What's your thought about this ?

always read with an opinion, thats me.

i used to be sceptical about the big bad pharms view, but after the revelations about gsk i believe them capable of anything.
however. the scientist how really found a cure for pd would get a nobel prize, so i can't see someone hiding such a discovery.

the biochemistry involved in pd research is TREEEEMMEEEEEENDDDOUSLY complicated and little bits of seemingly meaningless research place pieces of the 10,000 piece jigsaw.

from an amateur point of view - it is all coming together and an understanding of the ongoing process may not be far off. as for the initial cause - that may not actually matter to us what have got it (as ernie wise would put it).

charities too have an interest in preserving the problem they were set up for (present company excepted). but i cant see mjf squashing a cure if it existed.

as for GM1 - it has to be shown to be reasonably safe. there is no point in being cured of pd and getting cholera for instance http://en.wikipedia.org/wiki/GM1

safety takes time

end of opinion,
cheers

and sincerely, thanks Mr X for highlighting all the research

Turnip,

No thanks. I am happy to share every knowledge I have about interesting issues.

To get back to the GM1 story ... of course nobody wants cholera and it needs to be verified for safety. But that is exactly my issue. This GM1 is not something recently discovered. This product is really really known for a very long time. They are currently selling products for PD patients that were invented much later than GM1. All these products have been intensively tested in many clinical trials. GM1 wasn't treated in the same way, though they already did succesfull tests on monkeys in 1984. At this moment it should already have been fully investigated and known whether GM1 is disease-modifying and safe for people. At least, that is what I would expect from a drug that showed great results on monkeys in 1984.

Correct me if my reasoning is wrong, but I have the feeling that the community is not doing what it is supposed to do with GM1. Why are we sending money for research if this is how the PD community deals with our money ? Are we sending them money to avoid all real cures ? Are they using our money to find drugs that only deal with symptoms so some people can get rich at the expense of the funders ? I also have the feeling they are using PD patients are lab rats to test crazy stuff on them. They insert needles in the brain of PD patients, insert stemm cells with needles, Deep Brain stimulation ... all these things came much later than GM1. But they were all intensively tested. And seriously, isn't it wicked to have needles in your brain ? Isn't it crazy to have a pacemaker in your chest and electrodes in your brain ? Does it really make more sense to test gene therapies and deep brain stimulation on people then GM1 ? You understand my dilemma ?

And this doesnt only happen in PD research. The same happens in Azheimer with all this beta amyloid theories. I found out about a company that focused on tau instead of beta amyloid. The results were astonishing. Progression was slowed down by 80 % (Tau Cell Therapeutics). However, nobody talks about these results. Instead they keep ****** around about the beta amyloid path, over and over again. I don't consider such people even real scientists. A scientist can make a hypothesis. But if the experimental results show that his initial hypothesis was wrong, then or he tries to find an error in his experiment, or he admits his initial hypothesis was wrong and focuses on a new hypothesis. But no, in Alheimer community you can clearly see that all meds that are tested focus on beta amyloid; and none of them were succesfull. Only 1 company focuses on tau. Wouldn't you consider this as a waste of money ? The stubberness of some scientist is the reason a huge amount of money is literally getting thrown away in the garbage. And that's really frustrating, espcially if you are funding that research in some way.

I agree totally that the drug companies have a vested interest in ensuring research centres on drugs to treat the symptoms.
This is how their huge profits are generated.
Remember the hoo-ha when a large drug company that made a very profitable ant-acid concoction covered up, by means of bribes, the research that demonstrated that 99% of stomach ulcers were caused by a bacteria, helicobacter pylori, and could be cured by 2 weeks of antibiotics for about £3?
The surgeons involved in operating on patients with ruptured ulcers also knew and kept quiet.
The information was hidden for 10 years until the patent on the drug had run out.
All that suffering by so many people for someone's greed.
And people doubt that the huge pharmaceutical companies are still at it ?

very interesting points, which i can't really comment.

IT WOULD BE INTERESTING TO HEAR WHAT PUK RESEARCH HAVE TO SAY ABOUT THEM

(shouting so research can hear!)

Hi turnip,

No need to shout! We try to be as responsive as we can be, though it can be a bit of a struggle at 10pm.

As always, if you feel that we’ve missed something on the forum, you can write to us at forum(at)parkinsons.org.uk though you may have to wait until we get into the office to respond.

Katie from our Research team did respond to a question on GM1 ganglioside previously. You can find this answer here: http://bit.ly/UfJ2Kb

I have passed this thread to that team to see if there is anything they can add to this.

Ezinda

@ezinda: Katie did reply. But I considered it to be a very easy and weak reply.

Hi all,

Thanks for the interesting discussion.

As a research-based organisation, we continue to watch the progress of scientists around the world for advances that may benefit people with Parkinson's. And although GM1 ganglioside research has thrown up some interesting results, it’s certainly not the only promising avenue of Parkinson's research.

As we highlighted in the most recent issue of Progress magazine, there are lots of different and exciting prospects currently being investigated for Parkinson's - see www.parkinsons.org.uk/progress

As you've been discussing, it's not clear why further trials of GM1 ganglioside have not happened yet for Parkinson's. Clinical trials are very expensive (many many millions) so it could be that money is currently being raised. Trials also take a great deal of planning to get them right, so this can hold things up too if there is disagreement between researchers on how best to design the study.

We've emailed Dr Schneider who led the previous trial to see if he can shed any further light on this - and we'll share anything we hear back from him with you.

With regard to pharma companies - it's a common misconception that pharma companies are not interested in cure because they won't make money that way. This just isn't true. A better treatment or cure for Parkinson's (or Alzheimer's) would be very profitable and neurodegenerative conditions are a major focus for pharma as they affect an increasing number of people around the world.

Astra Zeneca recently announced a renewed focus on Parkinson's, Alzheimer's and other neurodegenerative conditions:

http://bit.ly/Si5IbO

Developing new treatments takes a huge amount of time, effort and money, which may come from companies or independent organisations such as charities or governments. And, ultimately, this investment needs to be paid back by sales of a safe, effective new drug.

We're working hard to make the research process as streamlined and efficient as it possibly can be, and also to raise the money we need to fund the projects that will get us there. But we can't do it alone.

I hope this helps!

Best wishes

Claire
(Research team)

Claire,

Thanks for your reply. I really appreciate your kindness in giving us a reply.

I do follow up your research paths. Not saying they are not promising. But at the moment, from all I read (and believe me, I read a lot), GM1 ganglioside is by far the most promising substance. It has shown disease-modifying characteristics on monkeys ... but even more, also on people. If one path deserves special consideration, then it is definitely the GM1 ganglioside part. And not only for PD. It seems to have beneficial effects on other neurodegenerative diseases too.

I appreciate you contacted Dr. Schneider. I hope he replies and that you can tell us more about his research and how he is planning to progress with it. I can imagine the lack of money to progress ... well, at least back in the 80's and 90's. However, there are so many Parkinson organizations nowadays ... I don't get why he didn't receive money from them. I read constantly of the MJFF handing out grants for research. Why didn't they do this for the GM1 ganglioside study ? It can't be because they are not aware of it. They are. I know because I contacted them.

Concerning the pharma industry ... look. The way you explain it, it makes it ridiculuous to believe in conspiracies. BUT ... if company A, B and C are making huge profits on their symptomatic relieving meds and then you have company D finding a cure ... company A, B and C know they will go bankrupt because company D has patent on the cure. The only way out for A,B and C is to lobby together to avoid company D releasing it's product (at least until their patents expire).

To conclude, many thanks for your reply. We hope to hear back from you once Dr. Schneider reacts on your email.

Hello all,

Dr Schneider has very kindly written a response to you all which I have posted on his behalf.

I hope this goes some way to explaining the complex (and often frustrating) road to discovering new drugs.

Best wishes

Claire
(Research team)
-----------------------------------------------

Dear Claire and members of the Parkinson’s UK Forum,

I have been alerted to the lively discussion on your Forum regarding GM1 and would like to give you my thoughts on the development of GM1 and what has been happening with this compound.

First, I have to say that I share the frustration of many others at the slow pace with which GM1 has been developed. First, a little bit of history and then some current events: I published my first paper with GM1 in 1989 in a mouse model of PD, showed that it worked in a primate model of PD in 1992, published the first clinical findings in PD patients in 1995 and 1998, and a follow-up study in 2010 of extended use of GM1 by PD patients.

I have recently concluded a relatively small (77 subjects) Phase IIa study in PD patients using a placebo controlled, delayed start design (a research design believed to provide information regarding potential disease modifying properties of a drug). These results, which have been presented at 2 scientific/medical meetings, have recently been submitted for publication. The main findings of the study are that: GM1 had significant beneficial effects on motor symptoms compared with placebo; over the 2.5 year course of the study, the data were suggestive of a possible disease-modifying effect; and long-term use of GM1 was safe.

With all of the promising results and good scientific rationale for the use of GM1 in PD, why has this not gone farther in terms of drug development?

That’s an excellent question with a very complicated response.

I think a reality of drug development is that not every promising drug gets developed and makes it to market and this can be due to a variety of complicated reasons. I will try to briefly summarize at least what some of the issues have been for GM1 and some of the problems I have encountered over the many years that I have been trying to push this therapy forward.

GM1 was produced by one company, Fidia SpA and Fidia held the patents for its production and use. During the early stages of my pre-clinical and clinical research, I collaborated with Fidia. Unfortunately, Fidia ran into a number of problems that eventually led to the demise of the parent company in Italy and its component in the U.S. (Fidia Pharmaceutical Corp.). One of the contributing factors was an attempt by some to discredit GM1 and Fidia by claiming that GM1 use caused a peripheral neuropathy called Guillain–Barré syndrome. Although the connection between GM1 use and Guillain–Barré syndrome has never been proven or validated, it cast Fidia and GM1 in a negative light. This hastened the demise of Fidia and unfortunately, caused other companies to shy away from trying to take over and develop GM1.

Adding to the problems, GM1 was extracted from cow brains and mad cow disease was also in the headlines, causing further reticence on the part of the pharmaceutical industry to get involved with GM1. The manufacturing process for GM1 was actually shown to inactivate the agent responsible for mad cow disease and although the product was considered safe to use, it was a very tedious and expensive process, which I believe gave the industry further reservations about commercial development of the product.

In the late 1990s, early 2000s, I worked with a biotech startup to try to develop GM1 and analogs of GM1 for use in PD and other disorders. The research was progressing but unfortunately, the company was running out of funding, decided to focus their business in a different direction, the project was abandoned, and the company eventually folded.

I was fortunate enough to obtain funding from the NIH to conduct the recent clinical trial I mentioned earlier, but I have not been able to attract funding to progress the basic research on GM that is still necessary to address some important issues relating to things like formulation and mechanism of action. I do believe it is possible to reformulate GM1 so that we can enhance its bioavailability and produce a product that does not need to be injected but I have not been able to attract the funding necessary to pursue this, nor have I been able to convince others to take up this work. I also believe that if we learn more about just how GM1 works to produce the clinical effects that I have observed in PD patients, is quite possible that we could find a better therapeutic target and design a more effective therapy based on the principles of GM1.

Unfortunately all of this takes time and money and there is a shortage of both. I have begun to explore an alternative therapy using sialidases to naturally increase GM1 levels in the brain. At this point, we do not know if this strategy will be successful. However, if it is successful, it may be possible to formulate this therapy in such a way so that it does not need to be administered directly to the brain.

So yes, working with GM1 has been a long, rewarding, and frustrating experience for me but I truly believe that my efforts have not been in vain and that ultimately, there will be GM1 or a GM1-based product available for PD patients. I agree that it cannot come soon enough.

Jay S. Schneider, Ph.D.