PPAR stimulator GW1514 (topical) for repairing accutane damage?

http://www.ncbi.nlm.nih.gov/pubmed/15102088

I took accutane 5 years ago and have permanent damage: Now my face has skin fragility and thinness, extreme dryness and wrinkling, inflammation and irritation, dyshesion and diminished waterproofing, as the skin barrier homeostasis has been disrupted, etc. etc.

about 1 year ago i started taking adderall for adhd. and this has made my skin condition worse.

i'm wondering if anyone knows anything about PPAR stimulators ...which stimulate seb glands and other relevant mechanisms. i did not realize that there are TOPICAL ppar stims. i have posted about internal treatments for diabetes, but a topical option seems more pragmatic and less risky, especially since my damage is mostly localized in the face.

the specific one i read about is called GW1514....







Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes.
Schmuth M, Haqq CM, Cairns WJ, Holder JC, Dorsam S, Chang S, Lau P, Fowler AJ, Chuang G, Moser AH, Brown BE, Mao-Qiang M, Uchida Y, Schoonjans K, Auwerx J, Chambon P, Willson TM, Elias PM, Feingold KR.

Department of Medicine, University of California, San Francisco, California, USA.
Erratum in:

J Invest Dermatol. 2004 Oct;123(4):806.
Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes.

Networking people with permanent dry/flakey skin from Accutane

I TOOK ACCUTANE 5 YEARS AGO AND NOW I HAVE ROUGH, DRY, FLAKEY, PARCHED, LEATHERY, SKIN WITH ACCELERATED WRINKLING.

I AM IRISH, SO I THINK I AM MORE VULNERABLE TO THIS THAN OTHER PEOPLE. AND THIS MAY EXPLAIN WHY SOME SAY THEIR SKIN "RETURNS TO NORMAL" AFTER ACCUTANE AND OTHERS EXPERIENCE PERMANENT CHANGES.

I HAVE BEEN TRYING TO RESEARCH THIS, AND I THINK THE ACCUTANE KILLS OFF CERTAIN MECHANISMS INVOLVED WITH THE SKIN BARRIER THAT DAMAGES THE SKIN SURFACE "SEAL" AND REDUCES ELASTICITY AND DETERIORATED COHESION.

ALSO, SOME OF MY HAIR IS PERMANENTLY DRY AND WIREY NOW.

I WANT TO NETWORK WITH OTHER PEOPLE THAT HAVE THESE ISSUES. I THINK IT IS SIMPLY A SMALL POPULATION OF PEOPLE WITH THIS PROBLEM (AGAIN I THINK CERTAIN PEOPLE ARE MORE VULNERABLE LIKE IRISH/ENGLISH/SCOTTISH SKIN) SO I THINK WE NEED TO CREATE A DEMAND FOR ATTENTION ON THIS PROBLEM. I AM HOPING TO AGGRESSIVELY IDENTIFY PEOPLE WITH ADVANCED KNOWLEDGE AND RESEARCH ON RELEVANT TOPICS. I HOPE THAT THERE WILL BE SOME TREATMENTS TAILORED FOR THESE SPECIFIC PROBLEMS, BUTA T THE VERY LEAST I THINK IT IS IMPORTANT TO UNDERSTAND AND PROPERLY DIAGNOSE THE PRECISE MECHANISMS THAT HAVE BEEN DAMAGED.

I HAVE IDENTIFIED MANY INDIVIDUALS IN THE RESEARCH FIELD WHO PROBABLY COULD FIGURE OUT THIS PROBLEM BEST, BUT I THINK I NEED A NETWORK OF PEOPLE TO WORK TOGETHER, SINCE MANY OF THESE PEOPLE ARE DIFFICULT TO ACCESS AND CONTACT. IT IS ALSO IMPORTANT TO PREPARE WHAT EXACTLY WE ARE ASKING FOR, AND THIS COULD INVOLVE FIGURING OUT WAYS TO QUANTIFY THE PROBLEMS WE ARE HAVING.

ANYWAY, IF YOU ARE HAVING THESE PROBLEMS AND INTERESTED IN WORKING TOGETHER, MESSAGE ME. THIS MAY TAKE MONTHS AND YEARS TO FIGURE OUT, BUT I WANT TO HAVE A SYSTEMATIC APPROACH AND TRY TO EDUCATE OURSELVES AS BEST WE CAN.

Diabetes meds to restore Sebum in post-Accutane, dried up/rough face?

Hi,

To be honest, reading a lot of these posts are unbearable. It just brings me back to wretched flashbacks of being on Accutane.

I have a high tolerance for stress and bad memories, but with that experience/time of my life/accutane, I really just shudder anytime a post here triggers a memory, and I just can't read it.

Anyway, I've been posting elsewhere and on other somewhat related forums, so I'm a bit lazy to re-type everything.

But in a nut shell:

Took accutane 5 years ago, permanently dried/shrunk my sebaceous glands (yes, I know others argue it does not permanently do this, but it did for me -- I don't remember my dose, but I am pretty tall guy so perhaps I was given a high dose, and it gave me TERRIBLE cystic acne, and I already had pretty sensitive/pale skin -- in fact, my dad's side of the family all has really bad skin). Anyway, my cheeks/forehead are terribly dry and rough like wood. Even my hair around the hairline (above ears, neckline) is very coarse and 'like straw'. My pores on my cheeks/forhead look HUGE and dried up/empty. I recently started taking Adderall (about a year ago) which makes my nose very oily, and makes other people break out, but my cheeks and forehead are still dry as the desert. My skin feels dead and leathery and lifeless -- my wrinkles on my forehead/cheek areas are coming in so fast, and the folds are so saggy because of the lack of retension in the skin.

I have tried everything: drinking tons of water, changing diet, used tons of lotions/moisturizers, staying out of sun, exercise, biotin, fish oil, omega three, etc.

Nothing helps, and in fact nothing seems to affect it at all. My face's moisutre system (sans my nose) feels completely fried. And it really does even feel different than before -- feels like I have a sunburn or something because of the leathery quality of my skin.

Dermatologists have been largely apathetic, but I haven't really been pushy about it since I was sort of in denial about the severity of it and how much it bothers me.

I have just began researching potential leads for treatment, and the first one I encountered involves agonists for PPARs (Peroxisome Proliferator-Activated Receptors). These are supposed to stimulate sebum (the oil produced by sebaceous glands). I do not understand it quite fully, but I am under the impression that the its effect on sebaceous glands is opposite that of Isotretinoin.

The specific study I first stumbled upon measured Sebum levels of diabetics using oral treaments from two groups:

Thiazolidinedione: 1) Pioglitazone; 2) Rosiglitazone
Fibrate: 1) Gemfibrizol; 2) Fenofibrate

Now, I'm not going to run out and pressure my physician to prescribe me one of these medications. But for the record, Thiazolidinedione boosted Sebum production by 37% while Fibrate production boosted it by 77%.

I just think that this medication and this particular mechanism (agonizing the PPARs, which in turn have several subtypes) sounds very promising as a start for my "investigation." If I can't fix it, I hope at the very least to figure out exactly what happened.

I am no expert, and I am in no rush to experiment with new chemicals on my body, but I am just trying to educate myself. Anybody have insights regarding this matter? I would greatly appreciate any information. Thanks

(title/authors)
Peroxisome Proliferator-Activated Receptors Increase
Human Sebum Production
Nishit R. Trivedi1,6, Zhaoyuan Cong1,6, Amanda M. Nelson1, Adam J. Albert2, Lorraine L. Rosamilia3,
Surendra Sivarajah4, Kathryn L. Gilliland1, Wenlei Liu5, David T. Mauger5, Robert A. Gabbay4 and
Diane M. Thiboutot1,3