A Human Folliculoid Microsphere Assay for Exploring Epithelial- Mesenchymal Interactions in the Human Hair Follicle

The search for more effective drugs for the management of common hair growth disorders remains a top priority, both for clinical dermatology and industry. In this pilot study, we report a pragmatic organotypic assay for basic and applied hair research. The patented technique produces microdroplets, which generate human folliculoid microspheres (HFMs), consisting of human dermal papilla fibroblasts and outer root sheath keratinocytes within an extracellular matrix that simulates elements of the hair follicle mesenchyme. Studying a number of different markers (for example, proliferation, apoptosis, cytokeratin-6, versican), we show that these HFMs, cultured under well-defined conditions, retain several essential epithelial–mesenchymal interactions characteristic for human scalp hair follicle. Selected, recognized hair growth-modulatory agents modulate these parameters in a manner that suggests that HFMs allow the standardized preclinical assessment of test agents on relevant human hair growth markers under substantially simplified in vitro conditions that approximate the in vivo situation. Furthermore, we show by immunohistochemistry, reverse transcriptase–PCR, and DNA microarray techniques that HFMs also offer a useful discovery tool for the identification of target genes and their products for candidate hair drugs. HFM thus represent an instructive modern experimental and screening tool for basic and applied hair research in the human system

A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40 mg modified-release capsules versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea.

Randomized controlled studies of combination therapies in rosacea are limited.Evaluate efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40 mg modified-release capsules∗ (DMR) versus IVM and placebo (PBO) for treatment of severe rosacea.This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA]=4) to either IVM and DMR (combination arm) or IVM and PBO (monotherapy).A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (-80.3% vs. -73.6% for monotherapy, p=0.032) and IGA score (p=0.032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving IGA 0 (11.9% vs. 5.1%, p=0.043)† and 100% lesion reduction (17.8% vs. 7.2%, p=0.006) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index and ocular signs/symptoms, and were well-tolerated.The duration of study prevented evaluation of potential recurrences or further improvements.Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in severe rosacea