P21 – is this a reason why AP works?

[Suzanne]

http://www.sciencedaily.com/releases/2011/09/110907124616.htm

“New ‘Bouncer’ Molecule Halts Rheumatoid Arthritis; Protective Protein Prevents Immune System from Ravaging Joints and Bones

ScienceDaily (Sep. 8, 2011)

Mom of teen daughter with Poly JIA since age 2. Current med: azithromycin 250 mg MWF.

[Suzy]

Suzanne…I saw this research also recently and wondered the same thing. Are they saying that Chloramphenico will increase p21 ? Am I reading that right? I’m glad you posted this ! This sounds like a good explanation for AP and a good avenue to further investigate…..

…..I meant to research this further, but got really busy with my Senior in high school ( AP classes are great for college credit early but carry a heavy load.) Just realized the acronym for my sons classes (Advanced placement AP ) is the same as ABx protocol. Wouldn’t that be the day where there’s an actual AbxP class taught? Lol

Anyway, I lost track of this story a few days back and I am glad you posted it…Thanks!

[Jan Lucinda1]

Suzanne- Interesting post about effects of doxy and mino.

Jan

[NancyB]

Suzanne,
I’m just learning about RA and that is a fascinating article…also, I’m impressed with your googling to find the correlation with P21 and mino!

I would think that the researchers/authors are aware of the connection with increased p21 expression and tetracyclines, but they don’t mention any substances that might do that…perhaps, they don’t even want it to be known? As the lead researcher said:
“This discovery opens up a new avenue for future therapies, which are greatly needed for rheumatoid arthritis.” …so they’ll be looking to “new” drug development.

This seems to be another link as to why the AP is successful. Thanks for posting…
Nancy

[Maz]

Hi Suzanne,

Thanks for posting your find! It’s nice to see this research is continuing to the next level as one always wonders what happens to researchers when they happen upon some find and whether or not their research grants then mysteriously dry up. With mention of the Feinberg School of Med, I recalled the earlier stages of this research had gone into the Winter 2010 eBulletin:

viewtopic.php?f=1&t=6049&p=53838&hilit=casper+the+ghost#p53838

What’s interesting about this Casper the Ghost molecule is that if some abx have some effect on this immune-modulating molecule, then it begs the question…why then do a good many RAers herx and do better on lower, pulsed doses, particularly those with more severe inflam and disease? One would think the opposite would be true and the higher the dose, the more effective the immune modulation. Research like this nags at me – there has to be some precipitating event to suddenly cause the shutting down of this molecule. There are some pretty clever infections out there that seem to bypass or hijack the gatekeepers of immune function with some pretty elaborate cloaking mechanisms, some believed to even be able to switch genes off and on. So, I’m scratching me head here…why not the “bouncer molecule” P21, too? Wouldn’t it be nice if these things all had simple, straighfwd answers?

A drug that could be developed to only target the malfunctioning part of immune function and leaves all else intact could well be a miracle drug for RA, but it still leaves those nagging questions….what tripped that wire in the first place? It’s sort of the same question that comes up for me when I read about stem cell therapy….for some it’s amazing at re-setting immune function, but there are also now studies coming out that tie this therapy (particularly embyronic stem cells) to tumor growth and for others, the therapy doesn’t “stick.” What else (the initial triggering element?) is there that is not being addressed?

[Lizz]

There is other new info on this from the company Vertex. I’m not internet savvy, but lots of you are, so go to Reuters.com and search Vertex. They have a new drug they are testing that targets a protein too with hopeful results. Hope this helps.

[Suzanne]

@Lizz wrote:

There is other new info on this from the company Vertex. I’m not internet savvy, but lots of you are, so go to Reuters.com and search Vertex. They have a new drug they are testing that targets a protein too with hopeful results. Hope this helps.

It’s a JAK inhibitor
http://www.vrtx.com/current-projects/drug-candidates/vx-509.html

Mom of teen daughter with Poly JIA since age 2. Current med: azithromycin 250 mg MWF.

[Suzanne]

@Suzy wrote:

Are they saying that Chloramphenico will increase p21 ? Am I reading that right?

That is how I read it, and that tetracyclines can also do the same thing.

AP also means Associated Press! Lots of ‘important’ APs out there!

Mom of teen daughter with Poly JIA since age 2. Current med: azithromycin 250 mg MWF.

[Suzanne]

@NancyB wrote:

I would think that the researchers/authors are aware of the connection with increased p21 expression and tetracyclines, but they don’t mention any substances that might do that…perhaps, they don’t even want it to be known?

I also thought they would be aware, but you never know. They are not researching an infectious cause, so maybe abx are not on their radar. Or like you said, they want something new to develop!

Mom of teen daughter with Poly JIA since age 2. Current med: azithromycin 250 mg MWF.

[Lizz]

Suzanne, it seems a JAK inhibitor from what i read leaves the immune system more intact. is that right?

[Suzanne]

@Lizz wrote:

Suzanne, it seems a JAK inhibitor from what i read leaves the immune system more intact. is that right?

That would not be my impression. My understanding is that Pfizer’s new oral RA med is also a JAK inhibitor:
http://www.reuters.com/article/2011/09/08/pfizer-arthritis-idUSN1E7851TQ20110908?feedType=RSS&feedName=companyNews&rpc=43

Mom of teen daughter with Poly JIA since age 2. Current med: azithromycin 250 mg MWF.

[Suzanne]

@Maz wrote:

What’s interesting about this Casper the Ghost molecule is that if some abx have some effect on this immune-modulating molecule, then it begs the question…why then do a good many RAers herx and do better on lower, pulsed doses, particularly those with more severe inflam and disease? One would think the opposite would be true and the higher the dose, the more effective the immune modulation.

Maz, you have a lot of the same questions that I do, but I do have a response to this one. APers also take a lower abx dose than would be used to treat an infection. Less is more, whether it is infectious or immune modulation. If it was straightforward either way, you could hit hard and be done. Such a mystery.

Mom of teen daughter with Poly JIA since age 2. Current med: azithromycin 250 mg MWF.

[Maz]

@Suzanne wrote:

Maz, you have a lot of the same questions that I do, but I do have a response to this one. APers also take a lower abx dose than would be used to treat an infection. Less is more, whether it is infectious or immune modulation. If it was straightforward either way, you could hit hard and be done. Such a mystery.

We’ll have to keep eyes/ears peeled on this research and see what evolves. Thanks again! 😉

[Suzanne]

Looks like someone is researching another chemo drug for it:
http://www.ncbi.nlm.nih.gov/pubmed/21906442

“Combination of AD5-10 and Epirubicin in Treating Rhumatoid Arthritis.” (Yes, that is pubmed’s typo!)

“Conclusion Epirubicin may coordinate with AD5-10 in inducing FLS apoptosis through affecting the levels of p53, p21, c-FLIP, and Bcl-2.”

http://en.wikipedia.org/wiki/Epirubicin

Mom of teen daughter with Poly JIA since age 2. Current med: azithromycin 250 mg MWF.

[Suzanne]

http://www.ncbi.nlm.nih.gov/pubmed/21898359

“The cyclin dependent kinase inhibitor p21 is essential for resolution of murine inflammatory arthritis via its c-terminal domain.”

“CONCLUSION:

These data are the first to reveal that p21 plays an important role in limiting the activation response of macrophages in an inflammatory disease such as RA. Thus, targeting p21 in macrophages may be crucial for suppressing the development and persistence of RA.”

Mom of teen daughter with Poly JIA since age 2. Current med: azithromycin 250 mg MWF.

[Author]

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