Gallo's theory and resources

[bellableu]

We just did, Doug.
Were you expecting a Christmas card?

*rimshot*

Smarty-pants!

[mrsmoof]

Picked out of Warren's net. Another piece in the Gallo jigsaw. Hopefully the finished piece will be an image that can be made sense of. The suggestion here that overexpression of TLR2 is peculiar to rosacea is contradicted elsewhere. Some thoughts about too that tacrolimus (Protopic) is a TLR2 antagonist. Protopic, as we know, provides few miracles.
Toll like receptors are quite the fashion; many drugs being developed to specifically target them.

http://www.ncbi.nlm.nih.gov/pubmed/21107351?dopt=Abstract

Abstract

A diverse environment challenges skin to maintain temperature, hydration, and electrolyte balance while also maintaining normal immunological function. Rosacea is a common skin disease that manifests unique inflammatory responses to normal environmental stimuli. We hypothesized that abnormal function of innate immune pattern recognition could explain the enhanced sensitivity of patients with rosacea, and observed that the epidermis of patients with rosacea expressed higher amounts of Toll-like receptor 2 (TLR2) than normal patients. Increased expression of TLR2 was not seen in other inflammatory skin disorders such as atopic dermatitis or psoriasis. Overexpression of TLR2 on keratinocytes, treatment with TLR2 ligands, and analysis of TLR2-deficient mice resulted in a calcium-dependent release of kallikrein 5 from keratinocytes, a critical protease involved in the pathogenesis of rosacea. These observations show that abnormal TLR2 function may explain enhanced inflammatory responses to environmental stimuli and can act as a critical element in the pathogenesis of rosacea.Journal of Investigative Dermatology advance online publication, 25 November 2010; doi:10.1038/jid.2010.351.

So maybe we need to inhibit or regulate TLR2? Since they are overactive! How do you inhibit or regulate TLR2? Are there any TLR2 inhibitors on the market today? Does Vitamin D play a role with TLR2? Demodex mites?

[GJ]

Are there any TLR2 inhibitors on the market today?

Some seem to think protopic is one. I'm not sure about that. TLRs are quite the thing. A nice table:

http://www.nature.com/nrd/journal/v1/n10/fig_tab/nrd914_T2.html

and the MCS18 stuff below is derived from a plant you might have in your garden. Helleborus purpurascens.

http://www.efic-congress.org/showabstract.php?abstract=527

I don't know the answers to those other questions.

[Brady Barrows]

Here is a link to the latest Gallo research on AMPs as of this date:

http://www.ncbi.nlm.nih.gov/pubmed/22158560?dopt=Abstract

[onelove]

http://www.clinicaltrials.gov/ct2/re...m=rosacea+ucsd
they just completed their trial. any new interpretations?

[buratino29]

I don't get it

All this theory of cathelicidins and kallikrein 5 being the true cause of inflammation – flushing ,was discovered in 2007.
Today as far as we can see, only university of California is in phase 0 of their trials aimed to target these enzymes or proteins.
Don’t you think it’s weird, that after 6 years since this has been discovered, we’ve got only one party involved in this type of research.
It’s usually the case when some phenomenon is discovered, you’ve got a dozen of labs trying to build their portfolio based on that. But there just university of California still in phase 0?

[peteroche]

Its simply just not good enough my friend ....

A bunch of wasters that's what they all are ......

for the last 19 years I heard a lot of talk and nothing ever happens ..

Its like a scratched record now and its beyond the joke

Whatever you hear from now on .....

should go in one ear and out the other ........

[buratino29]

Cromolyn Sodium

Interestingly, University of California that previously tested Aminocaproic acid for erythema, now enrolling patients to test Cromolyn Sodium. We can conclude that Aminocaproic acid failed.
But this time they specifically refer to papulopustular rosacea related redness which is not subtype 1 rosacea as far as I understand. Does that mean they give up on researching subtype 1 rosacea?
Cromolyn Sodium prevents the release of inflammatory chemicals such as histamine from mast cells. It is so called mast cell stabilizer and is already available in form of nasal spray (nasalcrom) or eye drops (Opticrom or Crolom) over the counter or with prescription.
Clearly, we’ve got two different directions here. Galderma’s Mirvaso works mostly by blocking alpha receptors. University of California appears to believe in downregulation of prostaglandins. Since prostaglandins are widely regarded as major catalysts for any type of inflammation that can occur in our body parts, they might be on the right track. Rosacea related redness is also an inflammatory effect.
Anyone interested in trying out Cromolyn sodium on your face? You might want to mix it with some cream for better spread.

http://www.clinicaltrials.gov/ct2/show/NCT01933464?term=rosacea+ucsd&rank=2

[redtere]

Interestingly, University of California that previously tested Aminocaproic acid for erythema, now enrolling patients to test Cromolyn Sodium. We can conclude that Aminocaproic acid failed.
But this time they specifically refer to papulopustular rosacea related redness which is not subtype 1 rosacea as far as I understand. Does that mean they give up on researching subtype 1 rosacea?
Cromolyn Sodium prevents the release of inflammatory chemicals such as histamine from mast cells. It is so called mast cell stabilizer and is already available in form of nasal spray (nasalcrom) or eye drops (Opticrom or Crolom) over the counter or with prescription.
Clearly, we’ve got two different directions here. Galderma’s Mirvaso works mostly by blocking alpha receptors. University of California appears to believe in downregulation of prostaglandins. Since prostaglandins are widely regarded as major catalysts for any type of inflammation that can occur in our body parts, they might be on the right track. Rosacea related redness is also an inflammatory effect.
Anyone interested in trying out Cromolyn sodium on your face? You might want to mix it with some cream for better spread.

http://www.clinicaltrials.gov/ct2/sh...ea+ucsd&rank=2

They have now published the results of the topical Aminocaproic acid trial.

Reduction in Serine Protease Activity Correlates with Improved Rosacea Severity in a Small, Randomized Pilot Study of a Topical Serine Protease Inhibitor.

http://www.ncbi.nlm.nih.gov/pubmed/24213369

It would be interesting to read the results but they charge $30 for the journal. I think someone on the forum has access to nature.com and has posted the pdf's of some of these journals here in the past.

[buratino29]

They have now published the results of the topical Aminocaproic acid trial.

Reduction in Serine Protease Activity Correlates with Improved Rosacea Severity in a Small, Randomized Pilot Study of a Topical Serine Protease Inhibitor.

http://www.ncbi.nlm.nih.gov/pubmed/24213369

It would be interesting to read the results but they charge $30 for the journal. I think someone on the forum has access to nature.com and has posted the pdf's of some of these journals here in the past.

Definately would be interesting to see those results.
But since they're using cromolyn sodium in their new trials, looks that they're not entirely happy with results

[fauxmccoy]

recently, i contacted the appropriate parties for consideration as a participant in one of the Gallo Labs clinical studies to evaluate the effect of a Cromolyn Sodium topical for rosacea.

this morning, i received the following response (i would like to note that the response took less than 48 hours, including the weekend).

Thank you for your email. We have actually reached our enrollment goals for both of those studies. We have another rosacea study that we will be starting sometime this summer though. It will also involve the use of a topical agent. If you are interested in possibly participating in this study, please let me know and I can send you more information once it becomes available.

clearly UCSD is working on this issue with some gusto. i'm glad to see it and will keep folks here informed.

[buratino29]

Thanks faux for your involvement.
But as I have already said, I’ve tried cromolyn sodium and it didn’t do much for my subtype1 rosacea.
Last year, 1 year prior to Mirvaso release I tried Brimonidine and reported here on forum brilliant initial results and subsequent rebound flushing. One year on and people’re reporting the same.
I hope one day they’re going to come out with something. As for cromolyn sodium, I don’t think it’s going to be a game changer.
But keep us informed if anything promising occurs.

[fauxmccoy]

i will not be participating on the cromolyn sodium study. as UCSD explained, they have a new topical ready for study this summer.

what gallo is writing about makes a lot of sense to me. mind you -- i do have some very bright family members in the medical community who can help me out. i really would not be surprised that rosacea will some day be classified as an auto immune disorder with a genetic link (excluding, perhaps, those with accutane or otherwise induced conditions). there is obviously more to be discovered than what gallo has released so far -- but i do think this is the most exciting discovery in a very long time. i have an unusual amount of auto immune disorders, only one had a cure and the the 'cure' was almost worse than the disease. i do not really expect a cure for rosacea in the forseeable future -- i do see hope, largely from gallo's researcch -- for real symptom relief however and i think it will lead to further understanding of the genesis of the disorder. we shall see. anyway, as i live in northern california and the occasional san diego getaway sounds lovely for this disabled housewife to escape home duties guilt free, i am happy to participate in UCSD's trials to the extent which i am able.

[buratino29]

i will not be participating on the cromolyn sodium study. as UCSD explained, they have a new topical ready for study this summer.

what gallo is writing about makes a lot of sense to me. mind you -- i do have some very bright family members in the medical community who can help me out. i really would not be surprised that rosacea will some day be classified as an auto immune disorder with a genetic link (excluding, perhaps, those with accutane or otherwise induced conditions). there is obviously more to be discovered than what gallo has released so far -- but i do think this is the most exciting discovery in a very long time. i have an unusual amount of auto immune disorders, only one had a cure and the the 'cure' was almost worse than the disease. i do not really expect a cure for rosacea in the forseeable future -- i do see hope, largely from gallo's researcch -- for real symptom relief however and i think it will lead to further understanding of the genesis of the disorder. we shall see. anyway, as i live in northern california and the occasional san diego getaway sounds lovely for this disabled housewife to escape home duties guilt free, i am happy to participate in UCSD's trials to the extent which i am able.

Hi faux. It's been a while. Did you by chance get involve in those trials with san diego uni.?