[RLSmi]

This is hot off the internet; published online yesterday.

The FASEB Journal, Published online February 27, 2007
Multifunctioonal tellurium molecule protects and restores dopaminergic neurons in Parkinson's disease models
Benjamin Sredini, Revital Geffen-Aricha,Wenzhen Duan, Mchael Albeck, Frances Shalit, Harry M. Lander, Noa Kinnnor, Ortal Sagi, Ammon Albeck, Sigal Yosef, Miri Brodsky, Dvoora Sredni-Kenisngsbuch, Talil Sonino, Dan L. Longo, Mark P Mattson and Gal Yadid

Abstract: In Parkinson's disease (PD) dopaminergic neurons in the substantia nigra (SN) become dysfunctional and many ultimately die. We report that the tellurium immunomodulating commpound ammonium trichloro(diethoxyethylene-O,O'-)tellurate (AS1011) protects dopaminergic neurons and improves motor function in animal models of PD. It is effective when administered systemically or by direct infusion into the brain. Multifunctional activities of AS101 were identified in this study. These were mainly due to the peculiar Tellur-IV -thiol chemistry of the compound, which enabled the compound to interact with cysteine residues on both inflammatory and apoptotic caspases, resulting in their inactivation. Conversely, its interaction with a key cysteine residue on p21-ras, led to its activation, an obligatory activivity for AS101-induced neuronal differentiation. Furthermore, AS101 inhibited IL-10, resulting in up-regulation of GDNF in the SN. This was associated with activation of the neuroprotective kinases Akt and mitogen-activated protein kinases, and up-regulation of the antiapoptotic protein Bcl-2. Inhibition of caspase-1 and caspase-3 activities were associated with decreased neuronal death and inhibition of IL-1 beta. We suggest that, because multiple mechanisms are involved in the dysfunction and death of neurons in PD, use of a multifunctional compound, exerting antiapoptotic, anti-inflammatory, and neuerotrophic-inducing capabilities may be potentially efficacious for the treatment of PD.(end of abstract)


This compound, AS101, is currently in Phase II clinical trials in cancer patients, and is described in this publication as nontoxic.

Too good to be true, or the long sought-for "Holy Grail" for PD treatment?

Robert

[ZucchiniFlower]

An older study on AS101, not AS1011:

Tellurium Compound AS101 Induces PC12 Differentiation and Rescues the Neurons from Apoptotic Death

D MAKAROVSKYa, Y KALECHMANa, T SONINOa, I FREIDKINa, S TEITZa, M ALBECKa, M WEILb, R GEFFEN-ARICHAa, G YADIDa AND B SREDNIa

aC.A.I.R. Institute, Faculty of Life Science, Bar Ilan University, Ramat Gan, 59200 Israel
bDepartment of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel

Address for correspondence: Dr. B. Sredni, C.A.I.R. Institute, Faculty of Life Science, Bar Ilan University, Ramat Gan, 59200 Israel. Voice: +972-3 531-8250; fax: +972-3 635-6041. srednib@mail.biu.ac.il
Ann. N.Y. Acad. Sci. 1010: 659-666 (2003).

Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Studies show that anti-apoptotic and neurotrophic agents are suitable candidates to prevent delayed cell death and/or restore neural function.

Here we present the nontoxic immunomodulating compound AS101, which has the ability to induce neurite outgrowth and neural differentiation in PC12 cells. The present study shows that components of the ras signaling pathway are crucial for AS101-induced PC12 differentiation.

These include p21ras and its downstream effectors, c-raf-1 and MEK, as well as PI3K. Moreover, these components mediate AS101-induced upregulation of p21waf, which is obligatory for AS101-induced PC12 differentiation. Furthermore, nitric oxide plays a significant role in these AS101 activities.

Finally, we show that AS101 prevents apoptosis of NGF-differentiated PC12 cells after NGF withdrawal

Taken together, these results suggest that AS101 induces PC12 cell differentiation and survival by activating the ras-ERK1/2 and ras-PI3K signal transduction pathways, as well as inducing NO production.

Our findings may be important in understanding the regulation of survival/apoptosis of neurons deprived of neurotropic support. Futhermore the data propose that AS101 may have clinical potential in the treatment of neurodegenerative disorders like Parkinson's disease.

http://www.annalsonline.org/cgi/cont...act/1010/1/659

[paula_w]

Well this grabs my interest because it is at the beginnning. Phase II ends many a treatment - it's difficult for treatments to survive Phase II. So (sorry) putting on my pipeliner hat- if you were in a match [yes I said match] with a patient agenda regarding what happens to this drug, against other "stakeholders'....as long as you immediately get educated about every aspect of the drug, bar nothing, you can then watch for things that aren't true, get patient opinion when it is possible. Note the classic "word statements that say absolutely nothing" Is there a website that teaches you all of them?

Ok so translating that to action - right after it is translated into English. this treatment will enter many databases - just learn everything

Accept translations of studies only from qualified medical consultants [but you knew that]

Note how close the press releases are to a significant vote anywhere. Always think 'why now'

Be open minded

See what happens.

Paula

[RLSmi]

It turns out that this "Brand New" drug has been around for 20 years! This group published an article in a 1987 issue of Nature entitled "A new immunomodulating compound (AS101) with potential therapeutic application."

ZF, I have not learned how to copy and paste article references with abstracts, so I typed that whole thing, including the "AS1101" typo. As Little Richard says in the Geico commercial, "SOMEBODY HELP ME!"

[ol'cs]

compounds(s) being tested and the paradigms being used to support the stated activity of these Te compounds. Now I really don't like being critical of ANYTHING that couls reduce or eliminate our suffering, I'm just critical of statements that are made, but "fizzle out" aftera bit more testing. IMHO, any substance which involves action in the caspace cycle of apoptosis, must be thoroughly studied because as we all know apoptosis inhibition anywhere in the body can lead to tumors. The body has a way of self healing, which sometimes means getting "rid of" cells that are not acting in the manner that they should given their genesis, lifetime, and function.
Once again, I am not criticizing this new "tack" at the compounds stated uses, just ever vigilant that we don't have a "worrisome" compound, in it's abilities to perform in he specific manner that is stated. After 10 years of reading the PD literature, nothing of this activity has "pannned out". I guess i'm a doubting Thomas, but how could I not be????? cs

[RLSmi]

Hair growth induction by the Tellurium immunomodulator AS101: association with delayed terminal differentiation of follicular keratinocytes and ras-dependent up-regulation of KGF expression. FASEB J. 18 400-402 (2004).

[ZucchiniFlower]

Cs, I read an article yesterday (I don't have time to search for the reference) that stated that the apoptosis in PD is different than one would expect; hopefully, it's different enough that a drug to counter it won't affect tumor cells.

I agree with you, though, that unintended consequences are the big elephant in the room, and we should be sceptical.

AS101 is also studied re: cancer. It's interesting that Gleevec, a drug for CML leukemia, also grows hair!

RLSmi, to copy and paste is easy. Highlight the text with your mouse, and go to the "edit" function on the left upper area on your screen. Drop down the menu and click on copy. Then place your curser where you want it to go, and drop down the same menu and click paste. Or use keyboard shortcuts: press control and c for copy and control and v for paste.

~Zucchini

[Curious]

another way to copy and paste:

use your mouse to hightlight the text. lfet click and drag your mouse over the text you want to copy. after it is highlighted, right click your mouse. the drop down menu should say copy ( unless the web site doesn;t allow right clicking)

click copy. then on the reply page here or what ever document, right click again. click paste.

i use this and the keyboard shorcuts zucchini posted.

[ZucchiniFlower]

WoW, Carolyn, thanks for the tip! I'll use it and pass it along.

~Zucchini