Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« The Galaxy Is Full of Gunk | Main | Thanksgiving Synthesis »

November 21, 2012

TauRx Goes Into Phase III For Alzheimer's

Email This Entry

Posted by Derek

I can't even count the number of e-mails I've gotten over the last few years asking about TauRx and their Alzheimer's program, which made a big splash back in 2008. Finally, there's some news to report. The company is starting Phase III clinical trials, and has announced new financing to see these through. The company is based in Singapore, and they're getting money from a large multinational company in the region.

Good for them. The tau-based therapy they're working on is a very interesting idea, and (of course) extremely significant if it actually works. I'm happy to see that it's going to get a real chance to prove itself, and I look forward to seeing the results. Their earlier compound ("Rember") was reformulated methylene blue, but they now seem to have an improved version to go ahead with (and not just in Alzheimer's, apparently).

I know I'll get more mail about this, but let me save time by telling those interested to go here, to a site run by TauRx about their clinical trials. It seems that they have started enrolling patients in North America.

Comments (19) + TrackBacks (0) | Category: Alzheimer's Disease | Clinical Trials


COMMENTS

1. barry on November 21, 2012 10:11 AM writes...

any company trying to deliberately build/buy an archive of "diverse small molecules" will find the occasional dyestuff hitting in a high-throughput assay. My experience has been that they all flunk Shoichet's "aggregator test" so far. Maybe this one's different? But I'd check that result three times.

Permalink to Comment

2. ablueman on November 21, 2012 10:33 AM writes...

This has to be the only trial where the placebo group are on API (8mg/day). I'll let you work it out ....

Permalink to Comment

3. luysii on November 21, 2012 11:42 AM writes...

#2 What's API (Aricept?)

Permalink to Comment

4. Anonymous on November 21, 2012 12:07 PM writes...

Active Pharmaceutical Ingredient

Permalink to Comment

5. anon on November 21, 2012 12:11 PM writes...

luysii I'm guessing its Active Pharmaceutical Ingrediant. Methylene blue has the side effect of making your urine turn green/blue and therefore a placebo has to do the same thing - so it has to be low dose methylene blue. I hope they have the doses right and don't see a massive "placebo" effect.

Isn't leuco just colourless i.e. reduced methylene blue. In which case its starting to look like some of the chlorpromazine type anti-depressants. Is it working through the reduced form with an effect on transmission or through the oxidised form as a tau detangler.

I'd hate to be running the bioanalytics on this - how do you stop the forms interconverting on the lc ?

Permalink to Comment

6. luysii on November 21, 2012 1:04 PM writes...

It is worth keeping in mind that methylene blue is a Nissl stain. Neurons (particularly long projection neurons to the spinal cord, and from the spinal cord to muscle) have huge cellular volumes. Although there is some protein synthesis from ribosomes in dendrites, most is carried out in the cell body which has to make the proteins for a huge cytoplasmic space (often 100 or more times larger than the visible cell body). This leads to huge amounts and clumps of ribosomes, visible in the light microscopy as Nissl substance. Nissl developed these stains a century ago, long before we even knew what a ribosome, RNA or DNA was. Nissl stains, such as methylene blue are positively charged and bind to the negatively charged phosphates linking the ribonucleotides together in RNA.

Something to keep in mind when you think of methylene blue or something like it having an effect on proteins. Methylene blue also inhibits guanyl cyclase, important in nitric oxide synthesis.

Hopefully the trial will work. We certainly need something better than what we have.

Permalink to Comment

7. Lane Simonian on November 22, 2012 1:16 AM writes...

Methylene blue also inhibits inducible nitric oxide synthase. Inducible nitric oxide combines with superoxide anions to form peroxynitrites. Peroxynitrites contributes to the hyperphosphorylation of tau proteins and mediates the nitration of those proteins so they cannot be reconstituted for proper neurotransmission (incidentally peroxynitrites nitrate amyloid plaques increasing their aggregation).

FASEB J. 2006 Jul;20(9):1431-42.
Peroxynitrite induces Alzheimer-like tau modifications and accumulation in rat brain and its underlying mechanisms.
Zhang YJ, Xu YF, Liu YH, Yin J, Li HL, Wang Q, Wang JZ.
SourcePathophysiology Department, Key Laboratory of Neurological Disease of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.

Abstract
To investigate the upstream effector that led to tau hyperphosphorylation, nitration, and accumulation as seen in Alzheimer's disease brain, and the underlying mechanisms, we bilaterally injected SIN-1, a recognized peroxynitrite donor, into the hippocampus of rat brain. We observed that the level of nitrated and hyperphosphorylated tau was markedly increased in rat hippocampus 24 h after drug administration, and these alterations were prevented by preinjection of uric acid, a natural scavenger of peroxynitrite.

Find the right peroxynitrite scavenger or scavengers and you not only slow the progression of Alzheimer's disease, you partially reverse it. What a happy note just before Thanksgiving!

Permalink to Comment

8. Anonymous on November 22, 2012 3:58 PM writes...

Wischik came up with Methylene Blue in 1994 or so and has since been pursuing it doggedly. He has not published any of his findings in peer reviewed journals, and many in the field think that he is off the mark (he appears to think the same about his peers). It would be very interesting to actually see the Phase II data.

In a field where no breakthroughs have been made in a decade, hope dies last.

Permalink to Comment

9. Debbie Johnson on November 25, 2012 2:07 AM writes...

That's awesome. I can't wait to see the results of this!

Permalink to Comment

10. Debbie Johnson on November 25, 2012 2:08 AM writes...

That's awesome. I can't wait to see the results of this!

Permalink to Comment

11. Anonymous on November 28, 2012 6:12 AM writes...

four 11C labels in one molecule?
a 1:1 molar ratio of 18F?
that rubbish made my day...

Permalink to Comment

12. Ricky Connolly on March 26, 2013 7:40 AM writes...

^ What he said.

Permalink to Comment

13. Quinoline on March 27, 2013 11:40 AM writes...

I think I learned something from 12.

Permalink to Comment

14. insidecircles on March 28, 2013 4:00 AM writes...

"{I will|I'll} {right away|immediately} {take hold of|grab|clutch|grasp|seize|snatch}
your {rss"

Well, if you must.

Permalink to Comment

15. auto pomoc lublin on April 12, 2013 1:27 PM writes...

Thank you ever so for you blog post.Much thanks again. Will read on...

Permalink to Comment

16. Elease Prado on June 21, 2013 12:54 AM writes...

likes is incredibly easy, you should not avoid above steps and save your Facebook Page Likes. Also check out Here you can check how to divert your Facebook Web page traffic to you Web page Connect with TricksWindow on

Permalink to Comment

17. Christoper Mattingley on August 1, 2013 3:40 AM writes...

Having the very good health and financial resources to travel with my wife as much as possible, to see more with the globe and meet more of its men and women.

Permalink to Comment

18. Tandra Pilkerton on September 29, 2013 3:01 PM writes...

not whenever they genuinely dont treatment about our survival which they dont it may be bullshit but when it does come about it could in all probability be somthing such as this . NO warning in any respect, thats why all of the main governments in the world are making underground bunkers which probably want do the job anyhow

Permalink to Comment

19. Fake taxi on November 24, 2013 11:55 PM writes...

I every time spent my half an hour to read this webpage's posts every day
along with a mug of coffee.

Permalink to Comment

POST A COMMENT




Remember Me?



EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
XKCD on Protein Folding
The 2014 Chemistry Nobel: Beating the Diffraction Limit
German Pharma, Or What's Left of It
Sunesis Fails with Vosaroxin
A New Way to Estimate a Compound's Chances?
Meinwald Honored
Molecular Biology Turns Into Chemistry
Speaking at Northeastern