5 replies to this topic

[03GT]

Thought some of you might appreciate this, I know I did. Unfortunately, there is no accurate mouse model for human acne so good luck getting through FDA trials with this.

Thesis: "The Innate Immune Protein Neutrophil Gelatinase-Associated Lipocalin is Involved in the Early Therapeutic Response to 13-CIS Retinoic Acid in Acne Patients"

Description: Acne is a disease that affects approximately 40-50 million Americans at any given time. For those with moderate to severe acne the choice of treatments is limited. The most effective agent for the treatment of acne is isotretinoin (Accutane®, 13-cis Retinoic Acid (RA)). 13-cis RA has teratogenic effects and its use is highly regulated. Although this drug has been used for over 25 years for acne, until recently little was known about its mechanism of action. Recent data indicate that the beneficial effect of isotretinoin in reducing sebum production is mediated by neutrophil gelatinase-associated lipocalin (NGAL). NGAL is a 25 kDa secreted protein with antimicrobial properties which has been reported to affect cell survival. Patients treated with isotretinoin have increased expression of NGAL in their sebaceous glands where it is induces apoptosis leading to reduced production of sebum and improvement in acne. This protein may be an important target for the development of alternate therapies to 13-cis RA.


The studies in this thesis indicate that NGAL is an important innate immune protein in the resolution of acne. NGAL’s increase on the skin surface of acne patients compared to the skin from normal volunteers has been identified through IHC and ELISA assays. Sebocytes treated with P. acnes have increased NGAL expression and secretion through a TLR-2 dependent mechanism. This increase in NGAL in acne skin and in sebocytes treated with P. acnes is much smaller than the increase observed with 13-cis RA treatment in patient skin and in cultured sebocytes. It has been determined that NGAL has antibacterial activity against P. acnes. The hypothesis is that the skin secretes NGAL as a response to the acne milieu but the levels are not sufficient to resolve acne. On the contary 13-cis RA increases NGAL to therapeutic levels that contribute to acne resolution. The current in vivo studies have revealed that significantly increased levels of NGAL can be recovered from patient skin as early as 1 week after beginning treatment with 13-cis RA and this increase correlates with a decrease in sebum and P. acnes levels on the skin. It has also been shown that NGAL and sebum levels plateau at approximately 8 weeks of treatment. These data indicate that NGAL is an important early response protein for 13-cis RA mediated acne resolution and may represent a target for the design of therapeutic alternatives to 13-cis RA.

Meeting Presentations

* 2007
Penn State College of Medicine Graduate Research Forum, Hershey, PA
Society for Investigative Dermatology 68th Annual Meeting, Los Angeles, CA
* 2008
Penn State College of Medicine Graduate Research Forum, Hershey, PA
Penn State Inflammation, Innate Immunity, and Disease Symposium, State College, PA
2nd International Conference on Sebaceous Gland, Acne, Rosacea and Related Disorders, Rome, Italy (poster award)
* 2009
Society for Investigative Dermagoloty 69th Annual Meeting, Montreal, Canada
Society of Pediatric Dermatology, Philadelphia, PA (oral)

Publications

Smith KR, Thiboutot DM (2008) Thematic review series: Skin Lipids. Sebaceous gland lipids: friend or foe? J Lipid Res. 49(2):271-81 PMID: 17975220

Lumsden KR, Nelson AM, Dispenza MC, Gilliland KL, Cong Z, Zaenglein AL, Thiboutot DM (2011) Isotretinoin increases skin surface levels of neutrophil gelatinase-associated lipocalin in patients treated for severe acne Br J of Derm [Epub April 2011] PMID: 21466536

[wheezle]

Interesting. I have chronic kidney failure, which is often associated with loss of proteins through urine. A Google search for NGAL yields mainly kidney-failure related sites, and it seems that amount of NGAL in the blood and urine is indicative of renal failure.

I wasn't able to determine this for certain, but I'm guessing that a lot, or more than usual, of NGAL in the urine is indicative of renal damage, and this would mean less NGAL in the bloodstream. I wouldn't be surprised if I were an example of this, especially since these studies seem to think that NGAL is such a reliable indicator.

Since NGAL is associated with the "upregulation of E-cadherin" as well, I wonder if E-cadherin could be relevant to acne.

E-cadherin seems to have a regulatory role in epithelial tissue production/maintenance and possibly in preventing metastasis in carcinomas. Seems pretty similar to out-of-control growth of epithelial skin cells and excessive keratinization. I hope NGAL yields some results in the future.

Thanks for posting this, 03GT.

Edit: Just noted that the referenced study specifically referred to cell apoptosis, citing it as the effective mechanism of RA. I agree with this, and it seems to make E-cadherin even more of a relevant possibility.

Edited by wheezle, 16 May 2011 - 12:06 AM.

[biggs881]

http://www.ncbi.nlm.nih.gov/pubmed/21564055

[03GT]

http://www.ncbi.nlm.nih.gov/pubmed/21564055

nice find

[facne]

This makes me wonder if there is some truth to the urine thing. Since NGAL is present in urine, does that mean it could help topically? I wouldn't try it b/c it's gross but just curious if it makes sense scientifically.

[03GT]

This makes me wonder if there is some truth to the urine thing. Since NGAL is present in urine, does that mean it could help topically? I wouldn't try it b/c it's gross but just curious if it makes sense scientifically.

lol, I just started trying that today...

Think of it like this, back in the day pork was considered disgusting because people would improperly cook it and end up getting parasites. Point is, it's all about knowledge and perspective. What is urine other than a concoction of chemicals that has been broken down from more complex chemicals. It's just chemicals...