Finacea and the Cause of Rosacea

Following on from a study that was able to show the reason that Finacea was able to adjust the inflammatory response in the skin, is this JAAD Poster session abstract.  This paper is looking at how the active ingredient in Finacea, azelaic acid can decrease the expression of 2 substances thought to be important in rosacea – kallikrein 5 (KLK5) and cathelicidin.

The lead author Richard Gallo is known for his research on cathelicidin. It is encouraging to see further research on how treatments might be proven and even developed based on the body of cathelicidin research.

Finacea seems to very much be the younger, less known brother to the market leader Metrogel, but the body of research linking Finacea to the ability to reduce processes active in rosacea might see Finacea gain a much bigger profile.

Azelaic acid gel alters kallikrein 5 and cathelicidin expression in epidermal keratinocytes, critical elements in the pathogenesis of rosacea

J Am Acad Dermatol 2010;60:AB1. Abstract P103, American Academy of Dermatology, 68th Annual Meeting, March 5–9, 2010, Miami, Florida (JAAD Poster Abstracts, March 2010 / Volume 62 / Number 3)

Richard Gallo, MD, PhD, VA San Diego Medical Center, San Diego, CA, United States; Kenshi Yamasaki, MD, PhD, Division of Dermatology, La Jolla, CA, United States

Recent observations have shown that facial skin from patients with rosacea produces excess amounts of the serine protease kallikrein 5 (KLK5), and abnormal forms of the antimicrobial peptide cathelicidin (CAMP).

In mice, abnormal CAMP and KLK5 expression influences inflammation, and administration of the forms of human CAMP found in rosacea results in inflammation, angiogenesis, and vascular telangiectasia.

In this study, we sought to further confirm the critical role of KLK5 and CAMP in rosacea by examining if the effects of a current human beneficial therapy correlated with changes in the expression of these genes.

We measured KLK5 in cultured normal human epidermal keratinocytes (NHEKs) and found that differentiated keratinocytes in high calcium media (1.6mM) greatly increased both KLK5 mRNA and protein compared to undifferentiated cells.

The addition of azelaic acid (AzA; 10-8 to 10-9M) to differentiated NHEKs significantly decreased KLK5 in media (vehicle; 91.26 6 22.58 ng/mL, 10-8M AzA; 41.69 6 15.08 ng/mL).

Total protease activity was also significantly less in media recovered from keratinocytes treated with 10-8M AzA.

Furthermore, mice treated once a day for 9 days with topical application of AzA gel 15% (Intendis; Berlin, Germany) showed significantly less KLK5 and CAMP mRNA compared with mouse skin treated with the vehicle alone (relative expression of KLK5 and CAMP was 55% and 32% of control, respectively).

In conclusion, because an excess of KLK5 and cathelicidin has been hypothesized to contribute to the development of rosacea, finding that an effective treatment for rosacea can decrease expression of these molecules further supports the involvement of KLK5 and cathelicidin in the pathogenesis of this disease.

REFERENCE
1. Yamasaki K, Di Nardo A, Bardan A,MurakamiM, Ohtake T, Coda A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 2007;13:975-80.

Commercial support: This study was funded by Intendis. Note: Intendis are the makers of Finacea.

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About the Author: David Pascoe started the Rosacea Support Group in October 1998. .

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