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Transcriptomics Analysis Indicates Trifarotene Reverses Acne-Related Gene Expression Changes.

Brigitte Dreno1, Rajeev Chavda2, Valerie Julia2

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Summary

Trifarotene, a topical retinoid, impacts acne by modulating genes involved in inflammation and cell migration. It uniquely affects proliferative macrophages, offering a novel mechanism for treating acne vulgaris.

Keywords:
acne (acne vulgaris)bioinformaticscellular expressiongene expressionpathophysiologytranscriptomicstrifarotene

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Area of Science:

  • Dermatology
  • Molecular Biology
  • Immunology

Background:

  • Trifarotene is a topical retinoid selective for retinoic acid receptor gamma.
  • It is approved for treating acne vulgaris.

Purpose of the Study:

  • To identify the molecular and cellular impact of trifarotene on acne papules using gene expression analysis.

Main Methods:

  • Open-label prospective study with subjects treated with trifarotene or vehicle.
  • Gene expression profiling of skin biopsies using Affymetrix technology.
  • In silico deconvolution of transcriptomics data using single-cell RNAseq.

Main Results:

  • Identified 67 genes modulated by trifarotene, involved in cellular migration, inflammation, and extracellular matrix reorganization.
  • Trifarotene treatment impacted SPP1+ macrophages, a subset of proliferative macrophages.
  • Gene expression changes were similar in trifarotene-treated and spontaneously resolving lesions.

Conclusions:

  • Trifarotene demonstrates a novel mechanism in acne treatment.
  • It affects both epidermal and immune components of acne pathogenesis.
  • The drug's impact on specific macrophage subsets suggests targeted therapeutic potential.