These cells produce an epidermal growth factor, epiregulin, which stimulates epidermal cell proliferation.[10] Epidermal cells are produced at a faster rate than the ability to slough the dead cells from the skin surface.[11] This overproduction of skin cells, in conjunction with angiogenesis, results in the initial appearance and continued progression of facial CP-690550 cost angiofibromas over time. Recent elucidation of the complex signaling relationship between the tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2) gene products and mTOR has led

to an explosion of research related to the use of mTOR inhibitors, such as rapamycin, in TSC. These mTOR inhibitors are showing promise in treating multiple tumor types, including renal angiomyolipomas

(AMLs), sub-ependymal AZD0156 concentration giant cell astrocytomas (SEGAs), and lymphangioleiomyomatosis CDK inhibitor (LAM).[12–15] Rapamycin is a naturally occurring antifungal macrolide, first isolated from Streptomyces hygroscopicus in 1965. Rapamycin binds with high specificity to mTOR, and binding results in inhibition of mTOR activity and ultimately in downregulation of cell growth.[16] Rapamycin has a molecular weight of 914.2 grams/mol, allowing for its absorption through the superficial layers of the epidermis to the deep dermal layer implicated in the development of facial angiofibromas. The primary goal of this study was to evaluate the safety of topical about rapamycin (0.003% and 0.015%) in patients with TSC. The secondary goal of this study was to evaluate the efficacy of the topical product for treatment of facial angiofibromas. Methods Patient Selection After approval was obtained from the institutional review board at the University of Texas Health Science Center (UTHSC) at Houston, study subjects were recruited from the patient population at the

Tuberous Sclerosis Center of Excellence at the University of Texas Medical School at Houston from January 2010 through August 2010. All subjects were over the age of 13 years and had a clinical diagnosis of tuberous sclerosis complex.[17] Subjects were excluded if they were currently pregnant, were using oral rapamycin, or had any form of immune dysfunction. After completing an informed consent document, willing participants who satisfied the inclusion and exclusion criteria (table I) were enrolled in the study. The study participants provided demographic data, including age, sex, and race, during the initial interview. Race/ethnicity was defined by the participants. Table I Inclusion and exclusion criteria for study participation Protocol Summary Upon enrollment, subjects were randomized and provided with a bottle of the investigational product. The investigational product contained one of three doses of rapamycin compounded with Skincerity®: (i) no rapamycin; (ii) 1 mg of rapamycin per 30 cc (0.003%); or (iii) 5 mg of rapamycin per 30 cc (0.015%).