Henne Sabrina K, Hochfeld Lara M, Bartmann Werner, Welss Thomas, Nöthen Markus M, Heilmann-Heimbach Stefanie
Institute of Human Genetics, School of Medicine & University Hospital Bonn, University of Bonn, Bonn, Germany.
Henkel Consumer Brands, Düsseldorf, Germany.
PLoS One. 2024 Dec 23;19(12):e0316128. doi: 10.1371/journal.pone.0316128. eCollection 2024.
Male-pattern hair loss (MPHL) is the most common form of hair loss in humans. Limited treatment options exist, which are not curative and vary in efficacy and invasiveness. Therapeutic and cosmetic hair growth stimulating agents that alleviate hair loss at a low risk of side effects are therefore of interest. The efficacy of hair growth-stimulating agents is mainly evaluated by hair comb tests and trichograms. These methods do not offer molecular insights, which can provide early insights into treatment response and may be useful in monitoring long-term compliance and efficacy. We propose a general concept for the molecular monitoring of hair growth stimulating agent treatment response in vivo, based on RNA and microRNA expression profiling before and during treatment. The molecular profile can be extended by individual genotype information to assess the impact of genetic constitution on treatment response. To test this methodological approach, 91 male participants with visible signs of and/or a family history of MPHL were assigned to four groups to investigate the effects of three hair growth stimulating agents versus placebo. mRNA- and microRNA-Seq was performed on plucked hair follicle samples before, after four days, and after six weeks of treatment. Genotyping was performed on DNA extracted from blood or saliva samples. Differential expression analyses identified 52 differentially expressed genes and 17 modulated pathways following treatment with the three hair growth stimulating agents. While the majority of effects were detectable after 6-week treatment, 23% of genes showed significant regulation after 4-day treatment. Integration with genetic data through pathway-based polygenic risk score analyses identified 5 associations between genetic background and treatment effects, pointing to a potential value of companion diagnostics for hair growth stimulating agents. Our data show that this molecular monitoring approach provides insights into hair growth stimulating agent treatment response as early as days within commencing treatment, and is suitable to monitor long-term treatment effects and compliance. Combined with genetic profiling, this approach may enable personalized prediction of treatment efficacy and compliance.
男性型脱发（MPHL）是人类最常见的脱发形式。现有的治疗选择有限，这些治疗方法无法治愈，且在疗效和侵入性方面存在差异。因此，具有低副作用风险且能缓解脱发的治疗性和美容性毛发生长刺激剂备受关注。毛发生长刺激剂的疗效主要通过毛发梳理试验和毛发图谱来评估。这些方法无法提供分子层面的见解，而分子层面的见解可以为治疗反应提供早期认识，并且可能有助于监测长期依从性和疗效。我们基于治疗前和治疗期间的RNA和微小RNA表达谱，提出了一种在体内对毛发生长刺激剂治疗反应进行分子监测的总体概念。分子谱可以通过个体基因型信息进行扩展，以评估基因构成对治疗反应的影响。为了验证这种方法，91名有MPHL明显体征和/或家族史的男性参与者被分为四组，以研究三种毛发生长刺激剂与安慰剂的效果。在治疗前、治疗四天后和六周后，对拔取的毛囊样本进行mRNA和微小RNA测序。对从血液或唾液样本中提取的DNA进行基因分型。差异表达分析确定了三种毛发生长刺激剂治疗后52个差异表达基因和17条受调节的通路。虽然大多数效应在6周治疗后可检测到，但23%的基因在4天治疗后显示出显著调节。通过基于通路的多基因风险评分分析与遗传数据整合，确定了遗传背景与治疗效果之间的5种关联，表明伴随诊断对毛发生长刺激剂具有潜在价值。我们的数据表明，这种分子监测方法在开始治疗后的数天内就能提供毛发生长刺激剂治疗反应的见解，并且适合监测长期治疗效果和依从性。结合基因分析，这种方法可能实现对治疗效果和依从性的个性化预测。
