GM1 Ganglioside


#1
"Treating Parkinson's disease patients with the experimental drug GM1 ganglioside improved symptoms and slowed their progression during a two and a half-year trial, Thomas Jefferson University researchers report in a new study published online November 28 in the Journal of the Neurological Sciences."

#2
Yes this is seemingly fantastic news:

http://www.sciencecodex.com/promising_drug_slows_down_advance_of_parkinsons_disease_and_improves_symptoms-102996

The thing I cannot understand is why this is not big news across all our newspapers and TV. I've only come across this in a couple of obscure websites so far. But as far as I can tell, this is the first double-blind, placebo controlled phase II study that has established statistically significant evidence of slowing disease progression.

If this is true, it is without question the biggest breakthrough since the advent of levedopa. You could actually argue it's more significant than levedopa because this slows disease progression whereas l-dopa only affects symptoms.

Perhaps the reason this isnt making headlines is that it's a university study funded by government, rather than a big pharma study with a huge PR department to push out the results.

Either way, I think this is really great news. Just a question of when phase III will get underway.

#3
WOW!

#4
For those that missed the previous GM1 ganglioside thread :

http://www.parkinsons.org.uk/pdsforum/posts.aspx?forum=research&topic=gm1-ganglioside&page=1

The doctor that performed this result confirmed me several months ago that his clinical phase II trial performed very good results. But I doubt there will be a clinical phase III with this. I contacted MJFF foundation and their reply gave me the feeling that they will NOT pursue this. It made me really angry. Instead, they are working now in pills that encourages your brain to produce more GM1. These pills are in preclinical phase. That's the funny thing about it. They go 15-20 years back in time. They don't know whether these pills will work, they don't know whether they will be safe ...

They came with many claims that GM1 is not practical. I had to laugh with their arguments. So is it a problem because it is not a pill ? So what about amarantus and their MANF ? GM1 is given as an injection, twice a day. This seems unpractical ? But inserting a tube with MANF in the brain is practical ? Then they complain about people getting the mad cow disease ... can someone show me scientific proof that GM1 leads to mad cow disease ? As far as I know there is no scientific evidence for that. And don't the trials proof that GM1 doesn't lead to mad cow disease ?

I don't know. What they are doing with GM1 is very fishy according to me. As I already said, I think big pharmas are blocking GM1. This is almost a real cure. Who needs all the old and new levedopa's and azilects if GM1 is provided to the patients ? What about all the companies with promising clinical trial I and II results ? They invested huge amount of money in their product. If GM1 gets to the patients all this money is lost and maybe even some companies have to get shot down. I am almost pretty sure this is why GM1 will never get to the patients. In this world: Money >>>>>>>>>> People.

#5
Hi all,

I’ve been taking a look both at your posts here and related papers.

Having read the paper in detail, I’m afraid that the results are not as positive as outlined by Dr Schneider in his press release. http://bit.ly/Z4CjHO

Let me explain. Essentially, the study had three phases.

First phase

In the first, half of the participants were treated with GM1 and the remainder with placebo.

The symptoms of the GM1 treated group improved significantly (as assessed by a standard clinical scoring system) while the placebo group continued to deteriorate, as did a 'comparison' group who also did not receive treatment.

Second phase – delayed start

After six months, the placebo group were changed over to GM1 – this was the 'delayed start' component of the trial or the second phase. While their condition improved, this was not to the same extent as those who had been on GM1 from the start.

This suggests either of two things:

• Firstly, the GM1 may have had a neuroprotective effect to slow down progression and because of this, those who were started on the drug later had a less profound effect.

• However, it could also be argued that GM1 has a purely symptomatic effect and that it is more effective when given at an earlier stage.

Third phase- ‘wash-out’ phase

The key phase however is the third one when the GM1 treatment was stopped in both groups after 120 weeks. This is referred to as the 'wash out' phase.

If the GM1 was protective, although the patients patient’s symptoms would deteriorate as the condition progresses, those who received GM1 from the start should continue to progress at a slower rate than those who only started the GM1 after six months. This was not the case.

After a further year off treatment, the conditions of both groups were equal so the both groups had deteriorated to the same level. In addition, although the comparison (non-treated) group were not followed after 96 weeks, an extrapolation of the rate of deterioration suggests that they would have been at the same clinical stage as those who had stopped receiving GM1 treatment.

This provides strong evidence that the effect of the drug was primarily symptomatic rather than protective. Unfortunately, the researcher did not refer to the wash-out phase in his press release.

The authors published a paper in the same journal in 2010 where they reported the results of an earlier five year study (http://to.ly/hNFv). Again the results were ambiguous and they could not draw any definite conclusions as to whether the effect of the drug is neuroprotective or symptomatic. In fact, they suggested that it was quite likely that GM1 was acting to make the remaining nerve cells more efficient.

You can be assured that we monitor all clinical research papers very closely and would be the first to report a study that shows a genuine neuroprotective effect. However, we do not wish to give false hope and unfortunately the results from this trial were not sufficiently robust to be considered as being neuroprotective.

I hope that this answers your questions, but please do not hesitate to contact me if you require further information.

Kind regards

Kieran

Dr Kieran Breen
Director of Research and Innovation

#6
Much appreciated Kieran. So, GM1 could be acting like L-Dopa in that it is relieving the symptoms of PD but the neurons are still dying. I wonder if Dr. Schneider could address that by measuring the rate of disappearance of sn cells in animal models during treatment with GM1 ? Trying to think of a different explanation..........it's possible GM1 is blocking the lethal action of a toxic molecule which still builds up to a steady state concentration sufficiient to kill the neuron once GM1 is removed..........

#7
Thx for the clarification, Dr. However, I am disapointed GM1 seems to not be neuroprotective or neurorestorative :cry:

#8
http://www.jneurosci.org/content/13/7/3104.full.pdf

#9
http://lib.bioinfo.pl/paper:17253773

The aggregation of alpha-synuclein is believed to be a key step in the etiology of Parkinson's disease. Alpha-synuclein is found in the cytosol and is associated with membranes in the presynaptic region of neurons and has recently been reported to be associated with lipid rafts and caveolae. We examined the interactions between several brain sphingolipids and alpha-synuclein and found that alpha-synuclein specifically binds to ganglioside GM1-containing small unilamellar vesicles (SUVs). This results in the induction of substantial alpha-helical structure and inhibition or elimination of alpha-synuclein fibril formation, depending on the amount of GM1 present. SUVs containing total brain gangliosides, gangliosides GM2 or GM3, or asialo-GM1 had weak inhibitory effects on alpha-synuclein fibrillation and induced some alpha-helical structure, while all other sphingolipids studied showed negligible interaction with alpha-synuclein. alpha-Synuclein binding to GM1-containing SUVs was accompanied by formation of oligomers of alpha-synuclein. The familial mutant A53T alpha-synuclein interacted with GM1-containing SUVs in an analogous manner to wild type, whereas the A30P mutant showed minimal interaction. This is the first detailed report showing a direct association between GM1 and alpha-synuclein, which is attributed to specific interaction between helical alpha-synuclein and both the sialic acid and carbohydrate moieties of GM1. The recruitment of alpha-synuclein by GM1 to caveolae and lipid raft regions in membranes could explain alpha-synuclein's localization to presynaptic membranes and raises the possibility that perturbation of GM1/raft association could induce changes in alpha-synuclein that contribute to the pathogenesis of PD.

#10
Unfortunately, GM1 ganglioside is one of the most misunderstood molecules on the planet. GM1 ganglioside was developed many years ago by an Italian pharma company called Fidia, from slaughter house cow brain. I'm sure you have all herd of a little disease in cattle called Mad Cow disease. Needless to say, Fidia was put out of the ganglioside business and much of their research was forced to limp to the finish line, including Parkinson's. GM1 is disease modifying in Parkinson's, but it turns out that Fidia had several GM1 derivitives (Liga 20 was one) that crossed the blood brain barrier better than the parent molecule. The current problem with GM1 ganglioside or any of the derivitives is that there is currently no source, anywhere. The FDA in the US won't allow anything of natural origin that comes from unknown slaughter house sources. We have been working for almost 20 years to try to remedy this problem. We have a closed, secure flock of sheep that have a genetic condition that results in the accumulation and storage of large quantities of GM1 in the brain and other tissues. The flock is free of Scrapie (like BSE) and each animals has complete records from birth to death. We market GM1 for research through a company called Avanti Polar Lipids. Our company is called Glycoscience Research Inc. and we hope to be able to provide safe raw material for ganglioside production and finally finish the work Fidia started many years ago. We have previously worked with a VC group in the states on Parkinson's but the project was terminated when it became clear that making lots of money quickly was more important than actually getting the drug approved for Parkinson's patients. We are currently working on Huntington's disease as the animals studies that have been completed with our GM1 in HD mice at Mass General look very impressive. HD is an orphan disease and would have a easier route to approval than Parkinson's. Also, there are only 30,000 HD patients so I don't need to raise quite as many sheep as we will need to for Parkinson's. But as I tell my friends suffering with PD, I won't quit until we have enough for everyone. We are trying to find grant money to complete the HD animal studies, but funding is tough to come by, and most folks no nothing about GM1. Hope this sheds some light on GM1 gangliside. It does work in Parkinson's and some of the derivitives work even better. With todays improve delivery systems, GM1 does hold significant progress for PD and HD, if we can only get it produced again. Larry Holler DVM, Phd