I stumbled upon some research that discovered mice who were Ganglioside deficient developed what looks like sporadic PD...as in they did not need be injected with toxins to induce the MPTP kind of Parkinsonism. This toxin coerced PD model has yielded much data, but I have always questioned it- these animal models were far from developing sporadic PD, but hey it's all we had.

Now, we have an animal model that looks and acts just like the human version we know so well; it involves neurodegeneration, motor symptoms, but most amazingly the mice show alpha-synuclein aggregation in the brain. This is not forced on them as it is with all other animal models of PD. This is just like us- so I am doing a happy dance thinking finally some real progress in solving this riddle. What brought this on? A lack of Ganglioside. I have read the wikipedia article and still don't know what it a Ganglioside is...

but learned we need the GM1 type. Look at what GM1 does:

...impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain.

Hey, it protects and encourages new neuron growth, and it passes the Blood Brain Barrier. Lookout GDNF

Then I get really excited when I read a couple abstracts on how mice in a different study with the older MPTP induced PD responded positively to treatment with GM1. Well, this is just mice, right. Once again, this a dead end.

Boy, I was wrong. Not only is there a study this year showing that PWP are Gangliodide deficient; better yet, we humans, respond really well to Ganglioside GM1 therapy. Needless to say I was thrilled to run across a study of this ganglioside in the treatment of PD and went to read over the abstract. I was astonished by what I read. This was not an early stage trial- it was a Placebo control trial showing both safety and efficacy; I quickly checked the date an read the trial results again. Here is the gist:

We have a natural substance that not only seems to halt degeneration but improved people in clinical trial long term over the course of five years. People in this study after five years treatment were better than baseline, that is off meds, five years later!

The date for this pub is 2010 but a five year study plus scant literature dating back to 1989 showing not only that this most likely would benefit us but people with Huntington's as well. This looks like Phase II of the trial.

We have what looks like a very promising disease modifying treatment that as a natural substance appears to be more important than dopamine loss and this was published two years ago. The substance can be taken orally and is tolerated well up to 1 gram daily though best range is 3-70 mg max.


GM1 ganglioside in Parkinson's disease: Results of a five year open study.

Is anyone else wondering why we do not know about this and feeling slightly punked? No one in the industry saw this as news worthy?

Am I over reacting? I hope others see something fundamentally wrong here. Why has this not been in press. When patients in a trial collectively fare BETTER off meds than they did five years upon taking this supplement doesn't that sort of tell us something beyond we need more studies. Does this have to do with the whole no patent no profit approach we have to improving the lives of those who suffer- right here and now- will it get tied up by the FDA again?

Sigh.

Laura

WOW, Laura. you discovered a therapy that just received funding from MJF foundation as an "innovative" therapy. madelyn

https://www.michaeljfox.org/foundati...?grant_id=1010

FUNDED GRANT
Enzymatic Degradation of Brain Complex Gangliosides to Increase Endogenous GM1 Levels: Potential Neuroprotective/Neurorestorative Therapy for Parkinson’s disease


GRANT ABSTRACT

Objective/Rationale:
Pre-clinical studies and clinical studies with GM1 ganglioside in Parkinson’s disease patients suggest potential symptomatic and disease modifying effects of GM1 on Parkinson’s disease. However, an alternative therapeutic approach to administering exogenous GM1 might be to enhance endogenous levels of GM1 in the brain. One potential way to do this is by administering sialidases, enzymes that convert complex gangliosides to GM1 while reducing levels of potentially harmful gangliosides.

Project Description:
We will evaluate the effects of administration of two different sialidases on the ability to protect the nigrostriatal dopamine system in a pre-clinical model of Parkinsonism (using the neurotoxin MPTP) and compare this to the response produced by exogenously administered GM1...

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
... If sialidase therapy is effective, it could be potentially administered to newly diagnosed Parkinson’s disease patients as well as to more advanced patients to slow the decline of functional ability and perhaps delay development of known treatment complications.

Anticipated Outcome:
This research will allow us to examine the extent to which the administration of sialidase may be a potential therapy for Parkinsons’s disease. We will learn whether pre-clinical models that receive MPTP and administration of sialidase have significantly higher dopamine levels and more dopamine neurons than pre-clinical models that receive MPTP and only a non-active vehicle. Results of these studies will tell us whether this therapy increases levels of GM1 and if effects of sialidases are similar to or better than the effects of administration of GM1 itself.


RESEARCHERS

Jay S. Schneider, PhD
Philadelphia , United States
PROGRAM NAME

RRIA 2012 (Rapid Response Innovation Awards)

ponderapharma.com/wp.../Endorphinate®-Science-Principles1.pdf

Starts getting interesting at page 4

http://www.bookidoc.com/text-id/49b20641h32i0

http://neurotalk.psychcentral.com/thread172141.html

Here is a list of research performed on GM1.

I am pretty sure disease modifying meds arrived:

https://www.michaeljfox.org/research...derisking.html

These are 4 companies working on targeting alpha-synuclien. Most of them just try to reduce a-synuclein in the brain. One of them is capable of unfolding the toxic aggregates to their normal state (and test on mice showed they actually got better --> 41 % improvement in motor skills in 6 months). The disease modifying meds are here, but they just need to be tested on safety. I almost dare to put my arm in the fire for this.

I had the same feeling when I first found out about this. The same for Alzheimer. This TauRx Pharmaceuticals achieved 80 % reduction in disease progression in a quite important clinical phase II. But they never speak about this. Then some researcher finds that K2 improved PD in fruit flies and suddenly this is the BIG news.

OK, I couldn't resist anymore. If people with PD, after 5 years of treatment with MG1 ganglioside, have better symptom scores than at the start of the treatment and it was proven that after 5 years of daily intake it was safe, then I want to know why the MJFox foundation didn't make this as their top priority. It seems to me that it not only relieves symptoms but also is neuroprotective. Given the importance of taking a neuroprotective medecine as early as possible, I just can't live with the fact that the MJFF doesn't try to push this product on the market.

So, I contacted the MJFox foundation to clarify why they aren't pushing for a clinical phase III on this. I am donating money to the organization to find a cure or to make life for people with PD much better. Therefore, I need to know why they aren't pursuing this path to its fullest. I will keep you updated about their reply.

ps: http://www.bioportfolio.com/resource...-Mice-And.html --> I also read something about PD patients having more antibodies against GM1.

Thanks for following upon all this! Apologies as well for not catching your original post; you have been sharing so much good stuff, I am not seeing it all

Yes, I don't get why research press releases are not more standardized. IT seems like most would want to take advantage of the publicity even Ivory Tower scientists. I see this as ground breaking, but that's me...I cried when Affiris started their vaccine trials for alpha-synuclein- it was the first time a potential treatment went to trial with the intent to modify disease.

I searched Clinical Trials . gov and located the most recent updates of 2010. Nothing about the cases of JBS. However, the status was "active, not recruiting" I am thinking of calling the lead researcher to see where this all stands now.

One thing about JBS; it is usually arrives on the heels of a viral infection and reverses if caught early. Do you know how many developed this and when?
I see it as anomaly; what are the odds of having two rare brain diseases?

Laura

Hi Laura and Diego,

My name is Stephanie and I'm the social media specialist with The Michael J. Fox Foundation. I've been following the thread for the past two days and took your questions to our staff researchers in the hopes of providing context.

In regards to research on GM1, Jay Schneider has presented positive results using GM1 as a therapeutic in PD patients and evidence that it may be disease modifying. There are several challenges to treating with GM1 including its ability to cross the blood brain barrier, not being orally available to take via a pill, and low potency, but the main issue is the current source of GM1. Currently to get GM1 for drug trials, you have to extract it from pig or sheep and there are issues when extracting natural products from these animals (scale up of enough product, risk of transmitting disease, etc) so what Dr. Schneider is doing is testing a compound that aims to increase levels of GM1 in the brain by increasing the normal synthesis of GM1. This project is testing whether he can see similar results using this new compound to using the GM1 itself. (This is what the MJFF Rapid Response grant is funding, and why it is referred to as "innovative.")

The Foundation is working to move as many ideas forward as we can, understanding that the process is complex and never as straightforward as we would like it to be.

As to why this was under reported in scientific trade outlets, we don't really know why. We can speculate that perhaps enthusiasm was dampened by the uncertain future of this approach (the source of GM1). Additionally, the timeline is fairly long at this point given that any new product would need be shown to be safe.

For our full research strategy, including priority areas, please visit our website.

Please let me know if you have any questions, I am happy to take them back to our researchers.

Diego, I'm not sure who you've emailed at the Foundation, but please feel free to contact me at socialmedia@michaeljfox.org.

Thanks,
Stephanie

So kind of you to clarify things, Stephanie. Thanks!

I have just one more question. It looks like Jay Schneider has also begun animal studies with a GM1 derivative; it is a semi-synthetic compound known as LIGA20. This was in the mid 90's; he had favorable outcome with this treatment as well. Do you know if LIGA20 is the treatment he is referring to in his current MJFF supported rapid response project?


Laura