Sharma Manju, Levenson Corey, Clements Ian, Castella Paul, Gebauer Kurt, Cox Michael E
The Vancouver Prostate Centre, Vancouver BC, Canada.
Santalis Pharmaceuticals, Inc., San Antonio TX, USA.
Front Pharmacol. 2017 Mar 16;8:125. doi: 10.3389/fphar.2017.00125. eCollection 2017.
Psoriasis, a chronic inflammatory skin disease marked by hyper proliferation and aberrant differentiation of keratinocytes, affects 2-3% of the world's population. Research into the pathogenesis of psoriasis has been hampered by the lack of models that accurately reflect the biology of the psoriatic phenotype. We have previously reported that East Indian Sandalwood oil (EISO) has significant anti-inflammatory properties in skin models and hypothesized that EISO might provide therapeutic benefit to psoriasis patients due to its anti-inflammatory and anti-proliferative properties. Here we present interim results from an on-going proof-of-concept Phase 2 clinical trial in which topically applied EISO is demonstrating to be well tolerated and helpful in alleviating mild to moderate psoriasis symptoms. This led us to evaluate the ability of EISO to affect the psoriatic phenotype using MatTek Corporation reconstituted organotypic psoriatic and normal human skin models. EISO had no impact on the phenotype of the normal skin tissue model, however, EISO treatment of the psoriasis tissue model reverted psoriatic pathology as demonstrated by histologic characterization and expression of keratinocyte proliferation markers, Ki67 and psoriasin. These phenotypic affects correlated with suppressed production of ENA-78, IL-6, IL-8, MCP-1, GM-CSF, and IL-1β. Demonstration of the ability of EISO to abrogate these psoriasis symptoms in well-characterized psoriatic tissue models, supports the hypothesis that the clinically observed symptom alleviation is due to suppression of intrinsic tissue inflammation reactions in afflicted lesions. This study presents a systematic approach to further study the underlying mechanisms that cause psoriasis, and presents data supporting the potential of EISO as a new ethnobotanical therapeutic concept to help direct and accelerate the development of more effective therapies.
银屑病是一种慢性炎症性皮肤病,其特征为角质形成细胞过度增殖和异常分化,影响着全球2%-3%的人口。由于缺乏能够准确反映银屑病表型生物学特征的模型,银屑病发病机制的研究受到了阻碍。我们之前曾报道,东印度檀香油(EISO)在皮肤模型中具有显著的抗炎特性,并推测EISO因其抗炎和抗增殖特性可能对银屑病患者有益。在此,我们展示了一项正在进行的概念验证2期临床试验的中期结果,在该试验中,局部应用EISO显示出耐受性良好,并有助于缓解轻度至中度银屑病症状。这促使我们使用MatTek公司重构的器官型银屑病和正常人皮肤模型来评估EISO影响银屑病表型的能力。EISO对正常皮肤组织模型的表型没有影响,然而,对银屑病组织模型进行EISO处理后,银屑病病理特征恢复正常,这通过组织学特征以及角质形成细胞增殖标志物Ki67和银屑蛋白的表达得以证明。这些表型变化与ENA-78、IL-6、IL-8、MCP-1、GM-CSF和IL-1β的产生受到抑制相关。在特征明确的银屑病组织模型中证明EISO能够消除这些银屑病症状,支持了以下假设:临床观察到的症状缓解是由于受累皮损中内在组织炎症反应受到抑制。本研究提出了一种系统方法来进一步研究导致银屑病的潜在机制,并提供了数据支持EISO作为一种新的民族植物药治疗概念的潜力,有助于指导和加速更有效疗法的开发。