Biolcati G, Aurizi C, Barbieri L, Cialfi S, Screpanti I, Talora C
Porphyria Center, San Gallicano Institute IRCCS, Rome, Italy.
Clin Exp Dermatol. 2014 Mar;39(2):168-75. doi: 10.1111/ced.12203. Epub 2013 Oct 25.
Hailey-Hailey disease (HHD) is a rare, chronic and recurrent blistering disorder, which is characterized clinically by erosions occurring primarily in intertriginous regions, and histologically by suprabasal acantholysis. Oxidative stress plays a specific role in the pathogenesis of HHD, by regulating the expression of factors playing an important role in keratinocyte proliferation and differentiation.
Given the significance of oxidative stress in HHD, we investigated the potential effects of the antioxidant properties of an α-MSH analogue, Nle4-D-Phe7-α-MSH (afamelanotide), in HHD lesion-derived keratinocytes.
Treatment of HHD-derived keratinocytes with afamelanotide contributed to upregulation of Nrf2 [nuclear factor (erythroid-derived 2)-like 2], a redox-sensitive transcription factor that plays a pivotal role in redox homeostasis during oxidative stress. Additionally, afamelanotide treatment restored the defective proliferative capability of lesion-derived keratinocytes. Our results show that Nrf2 is an important target of the afamelanotide signalling that reduces oxidative stress. Because afamelanotide possesses antioxidant effects, we also assessed the clinical potential of this α-MSH analogue in the treatment of patients with HHD. In a phase II open-label pilot study, afamelanotide 16 mg was administered subcutaneously as a sustained-release resorbable implant formulation to two patients with HHD, who had a number of long-standing skin lesions. For both patients, their scores on the Short Form-36 improved 30 days after the first injection of afamelanotide, and both had 100% clearance of HHD lesions 60 days after the first injection, independently of the lesion location.
Afamelanotide is effective for the treatment of skin lesions in HHD.
黑利-黑利病（HHD）是一种罕见的慢性复发性水疱性疾病，临床特征主要为主要发生在间擦部位的糜烂，组织学特征为基底层上棘层松解。氧化应激通过调节在角质形成细胞增殖和分化中起重要作用的因子的表达，在HHD的发病机制中发挥特定作用。
鉴于氧化应激在HHD中的重要性，我们研究了α-MSH类似物Nle4-D-Phe7-α-MSH（阿法美拉肽）的抗氧化特性对HHD病变来源的角质形成细胞的潜在影响。
用阿法美拉肽处理HHD来源的角质形成细胞有助于上调Nrf2[核因子（红细胞衍生2）样2]，这是一种对氧化还原敏感的转录因子，在氧化应激期间的氧化还原稳态中起关键作用。此外，阿法美拉肽处理恢复了病变来源的角质形成细胞有缺陷的增殖能力。我们的结果表明，Nrf2是阿法美拉肽信号传导减少氧化应激的重要靶点。由于阿法美拉肽具有抗氧化作用，我们还评估了这种α-MSH类似物在治疗HHD患者中的临床潜力。在一项II期开放标签试点研究中，将16mg阿法美拉肽作为缓释可吸收植入制剂皮下注射给两名患有许多长期皮肤病变的HHD患者。对于这两名患者，在首次注射阿法美拉肽30天后，他们的简明健康状况调查问卷-36评分有所改善，并且在首次注射60天后，两名患者的HHD病变均100%清除，与病变位置无关。
阿法美拉肽对治疗HHD的皮肤病变有效。
