http://www.taurx.com/tau.htm

At first this might not be related to PD ... but it is.

You may all know that if you start searching for PD related articles, you also end up in research articles concerning other neuordegenerative diseases. So I also tend to read articles about Alzheimer. In Alzheimer scientist are always talking about beta amyloid protein. However, I seriously don't understand Alzheimer scientists. I know about a vaccination study they once did (I think around 2002 or so) and that was partly failed because people died from it. But a certain amount of them were lucky enough to have antibodies against beta amyloid. After many years of following them, the results were a bit dissapointing. The results showed a bit disease modification, but it was not spectacular. So these results could already give you the feeling that targeting of beta amyloid was not the big hope for Alzheimer patients.

However, despite this knowledge scientists kept hoping on the beta amyloid theory. They tested flurizan in the biggest clinical phase III trial ever conducted on Alzheimer patients. It costed 200 million dollars !!! Result: no disease modification. So 200 million dollars thrown in the garbage bin. Yesterday there was this article saying that people with a gene that makes them have 40 % less beta amyloid are protected against Alzheimer. Scientists were relieved because this shows they beta amyloid theory must have some validity.

For heaven's sake !!! This kind of attitude makes me really ****** off. Scientists are so stubbered !!! How much proof do you need that the beta amyloid path is not the holy grail in Alzheimer ??? I read an article, published in february of this year showing that mice genetically modified to produce lots of human tau protein get alzheimer because the tau protein goes from neuron to neuron like a prion and destroying each neuron on its path. So doesn't it make more sense to target the tau protein ??? It is not like the tau protein has never been known. They know about its relation with Alzheimer from the 80's already !!!

Anyway, TauRx Pharmaceuticals is a company that finally targets the tau protein. Finally !!! And on their website they put their results from their clinical phase II trial:

This study provided the first clinical indication that treatment with the Company’s proprietary Tau Protein Aggregation Inhibitors holds promise in modifying the progression of AD. rember™ showed evidence in the phase 2 trial of a significant reduction in the rate of clinical decline: 80% by weeks 50 and 102 of this trial, relative to controls, as measured using psychometric tools. Functional neuroimaging results from the trial supported the psychometric data: in patients exposed to rember™, the loss of function occurring in the areas of the brain known to be particularly affected by the Tau-tangle pathology of disease was eliminated over 6 months. Functional brain scan benefits seen at 6 months were predictive of clinical benefit at 12 months.

I realize this is only a clinical phase II trial, and not a phase III. But an 80 % reduction in decline over 102 weeks ??? That is amazing. Can people with PD get a similar reduction in decline if clumped alpha-synuclein is targeted ? Based on the studies on animals tau attacks the neurons in the same was as alpa-synuclein does. So I can't wait to see the clinical phase III trial for Alzheimer. The good thing is that the same company also has a product in their pipeline to target alpha-synuclein. For sure, I will put a lot of focus on the alzheimer results of this company because of the mechanism related to PD.

[JKJK]

Diego, you are right: an 80% reduction in decline over 102 weeks is amazing!

Although it was a Phase 2 trial, it involved 321 patients, and that made the AD rember trial the largest Phase 2 clinical trial of a disease modifying treatment conducted to date. Results were statistically significant.

In the scientific circles, the chief scientist of TauRx Prof Wischik who is also the co-founder, has been known to be dogged in his singular pursuit of targeting the tau protein for decades. Few believed him as the scientific community was too heavily invested in the beta amyloid path despite the way being littered with failures.

I would agree with you that AD, PD and even FTD are all related.

I found the discussion in Feb this year in the website Corante In The Pipeline pretty interesting and educational, especially the comments posted by “sct” in this article “Tau Spreads On Its Own?” (Feb 7, 2012). Sorry, unable to post URL as I’m a newbie here. I’m sure googling will get you there.

The AD Phase 3 trial doesn’t seem far off, using an improved version of rember named LMTX:

"A closely held company, TauRx, based in Singapore, is developing drugs based on the tau model. TauRx’s tau aggregation inhibitors have been tested in Phase 2 clinical trials, and the company plans to make an announcement about its Phase 3 clinical trials later this year, said Claude Wischik, the executive chairman and co-founder of the company, in a telephone interview. " From Bloomberg(dot)com dated July 12, 2012.

Hopefully, the world will now get a real cure for AD, PD and other taupathies. Exciting times ahead!

[lurkingforacure]

I have often thought of the similarity between several neuro diseases, Alz. and PD being in the forefront.

It is no coincidence, then, that TauRx's Rember is methylene blue (see their website post you shared where they state this, but many knew that already), they are now working with a newer version of it, and the link Rick posted recently is about methylene blue being researched for PD in the spring of
2011, with results quite impressive on the rodent subjects. Again, the common theme is MB, and the results are all very positive.

I had never heard that MB was "poorly tolerated" as the TauRx site mentioned, nor that it had less than optimal bioavailabililty. MB has been used for decades, repeat, decades, on people, including the US military, and I have never heard of any such issues. Now, perhaps it doesn't cross the BBB so well, although I doubt that since one of the side effects of taking it is turning the whites of your eyes blue....seems like if something could do that, it could get across that pesky BBB.

Thanks for sharing this. I think anything that helps with Alz. will help understand PD and vice versa.

[ssharonec]

Abstract :Morris M, Koyama A, Masliah E, Mucke L (2011)
Many neurodegenerative diseases are increasing in prevalence and cannot be prevented or cured. If they shared common
pathogenic mechanisms, treatments targeting such mechanisms might be of benefit in multiple conditions. The tau protein
has been implicated in the pathogenesis of diverse neurodegenerative disorders, including Alzheimer’s disease (AD) and
Parkinson’s disease (PD). Tau reduction prevents cognitive deficits, behavioral abnormalities and other pathological changes
in multiple AD mouse models. Here we examined whether tau reduction also prevents motor deficits and pathological
alterations in two mouse models of PD, generated by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) or
transgene-mediated neuronal expression of human wildtype a -synuclein. Both models were evaluated on Tau+/ +, Tau+ /– and Tau–/–
backgrounds in a variety of motor tests. Tau reduction did not prevent motor deficits caused by 6-OHDA and slightly
worsened one of them. Tau reduction also did not prevent 6-OHDA-induced loss of dopaminergic terminals in the striatum.
Similarly, tau reduction did not prevent motor deficits in a-synuclein transgenic mice. Our results suggest that tau has
distinct roles in the pathogeneses of AD and PD and that tau reduction may not be of benefit in the latter condition.

Ssharonec, thanks for the info. I never thought of tau protein to be involved in PD. It is good this research confirms tau is not involved in PD. Now, we know for sure this is not the case, which is wonderful to know.

The tau protein is not the link between AD and PD. The mechanisms involved in AD and PD seem the common link. In AD tau protein spreads from neuron to neuron and leaving a thrace of devastation. In PD you have the same mechanism but it is caused by alpha-synuclein instead. At least, this is what scientists think. Given the fact that the tau targeting rember could reduce AD progression with 80 %, it is not weird to believe a similar reduction could be obtained targeting alpha-synuclein ... of course if alpha-synuclein is the cause of PD progression (which it most probably is).

This means the current PD vaccin trial of Saffiris is very hope giving to the PD community. Also the PD candidate from Remynd is very hope giving. What is even more hopefull is a combination between alpa-synuclein targeting and growth factors. Maybe this combination could halt or even slightly improve PD.

Call me optimistic, but I really see a bright future ahead for PD patients.