Question

修饰的HSP70i可防止T细胞介导的色素沉着。此外，他们还表明HSP70i在白癜风小鼠模型以及白癜风患者中诱导炎性DC表型，这是脱色所必需的[242，243]。有趣的是，突变体HSP70iQ435A已被证明可以预防和逆转不同的白癜风小鼠模型中的色素沉着。这些发现表明HSP70在白癜风沉淀中的重要作用，靶向HSP70i可能是治疗白癜风的一种有前景的方法[242] [243] [244]。...

...有趣的是，突变体HSP70iQ435A已被证明可以预防和逆转不同的白癜风小鼠模型中的色素沉着。这些发现表明HSP70在白癜风沉淀中起重要作用，靶向HSP70i可能是治疗白癜风的一种有前景的方法[    Mosenson et al. [242] reported that modified HSP70i prevents T cell-mediated depigmentation. In addition, they have also shown HSP70i induces an inflammatory DC phenotype in both vitiligo mouse models as well as in vitiligo patients, which is necessary for depigmentation [242,243]. Interestingly, mutant HSP70iQ435A has been shown to prevent and reverse the depigmentation in different mouse models prone to vitiligo. These findings indicate a vital role of HSP70 in precipitation of vitiligo and targeting HSP70i might be a promising approach towards the treatment of vitiligo [242][243][244]. ...

... Interestingly, mutant HSP70iQ435A has been shown to prevent and reverse the depigmentation in different mouse models prone to vitiligo. These findings indicate a vital role of HSP70 in precipitation of vitiligo and targeting HSP70i might be a promising approach towards the treatment of vitiligo [242][243][244]   https://www.researchgate.net/publication/235750450_Mutant_HSP70_Reverses_Autoimmune_Depigmentation_in_Vitiligo

Answer 1

SCENESSE® (afamelanotide 16mg)

The SCENESSE® (afamelanotide 16mg) Package Information Leaflet (English PDF) can be accessed here. The SCENESSE® (afamelanotide 16mg) Summary of Product Characteristics (English PDF) can be accessed here. Information in languages other than English available on the European Medicines Agency’s website here (external link).

SCENESSE® (INN: afamelanotide) is CLINUVEL’s proprietary first-in-class photoprotective drug. The drug has been  approved for marketing authorisation under exceptional circumstances by the European Medicines Agency for the prevention of phototoxicity in adults with the orphan disease erythropoietic protoporphyria (EPP). In June 2018 CLINUVEL submitted a new drug application with the US FDA seeking marketing authorisation for SCENESSE®. Further studies of SCENESSE® are underway as a repigmentary agent in vitiligo.

In October 2018, CLINUVEL announced that a Phase IIa proof of concept study (CUV040) evaluating SCENESSE® in variegate porphyria (VP) is expected to start patient treatment in the northern hemisphere spring of 2019.

SCENESSE® (pronounced “sen-esse”) acts by increasing the levels of melanin in the skin; and shields against UV radiation (UVR) and sunlight. SCENESSE® is delivered via a subcutaneous dissolving implant approximately the size of a grain of rice. Increased pigmentation of the skin appears after two days and lasts up to two months.

Alpha-Melanocyte Stimulating Hormone (α-MSH) is a naturally occurring peptide hormone which is released by skin cells in response to the stimulation by ultraviolet radiation (UVR). α-MSH has a very short half-life (seconds) in the blood stream, sufficient to reach and stimulate other skin cells (melanocytes) which in turn produce and release melanin, a dark brown pigment. Melanin is known for its photoprotective effect.

Comments

近日，南加州色素沉着和白癜风研究所宣布，其研发的白癜风药物SCENES SE已经进入临床试验的最终阶段。研究负责人Pearl E. Grimes在皮肤病的治疗方面有近半个世纪的研究经验，她曾于1974年获得华盛顿大学圣路易斯医学院皮肤病学博士学位，此后，她曾先后在霍华德大学、加州大学洛杉矶分校等机构从事皮肤病学的研究工作，直到1990年，她决定将自己的研究成果应用于实际治疗，于是创立了南加州色素沉着和白癜风研究所。

在创立研究所后，Pearl E. Grimes就开始着手研发治疗白癜风的药物。经过多年的研发，研究人员终于在2000年制出可以激活皮肤黑色素细胞产生和扩散的注射药物SCENES SE。此后，研究人员进行了为期十多年的试验，证明了SCENES SE可以增加皮肤黑色素含量，而它与目前最流行的窄波紫外线光疗法NB-UVB相结合时，可以将后者原本需要18个月的疗程缩短至6个月，并且可以减少每次紫外线辐射的剂量，此外，该药物的安全性也能满足临床要求。

试验的成功也使得这款药物于2010年获得FDA进行临床试验的批准。此后，该研究所和澳大利亚生物制药公司Clinuvel达成合作，联合在位于美国和欧洲的6个白癜风研究中心对120名患者进行临床试验。截至目前，前三期的试验结果均与此前试验一致。

由于此前获得的试验结果较为喜人，SCENES SE也在2016年率先在意大利获得批准来治疗紫质症。这种疾病的患者紫质代谢异常，从而使其皮肤对阳光极为敏感，在阳光下就会起水泡、溃烂甚至造成死亡。而SCENES SE在增加皮肤黑色素含量后即可阻紫外线和阳光对皮肤的辐射。如果最终的临床试验进展顺利，该药物也许很快就能进入治疗白癜风的临床应用阶段。

其实，除了Pearl E. Grimes博士之外，全球范围内也有很多科学家在潜心研究治疗白癜风的方法，并且也都各自取得了不俗的成绩。

比如，在2013年3月，德国莱比锡大学再生医学转化中心的研究人员就研发出一种自体细胞疗法。具体而言，研究人员发现人类头发毛囊的外毛鞘含有干细胞，在实验室中，这些干细胞可以在4周内被诱导培养为黑色素细胞。在将这些黑色素细胞植入到小鼠体内后发现，它们对小鼠是无害的。目前，研究人员正在对这些细胞的功能、迁移行为以及与周围细胞的互动进行分析，同时也在对它们的稳定性和集落形成过程进行研究。接下来，他们将会在人类志愿者身上进行临床试验。

再比如，在2014年2月，美国洛约拉大学Stritch医学院的Caroline Le Poole教授就曾制造出一种基因改造蛋白。这种蛋白是对于引发白癜风自身免反应的诱导热休克蛋白70（HSP70i）的氨基酸序列进行了遗传学改造，从而得到了突变型HSP70i。在将这种蛋白接种到白癜风小鼠模型体内后，小鼠的皮毛重新变为了黑色。目前，研究人员正在利用这种突变型HSP70i蛋白进行临床试验。

相信随着科学家们研究的进一步深入，在不远的将来，全世界的白癜风患者们就能不用忍受植皮手术或光照疗法的折磨，而是可以针对自身情况在众多药物中选择最适合自己的一种。

Answer 2

SCENESSE® is a chemical analogue of α-MSH and is a linear peptide with 13 amino acids. Two amino acids present in α-MSH have been changed and amplified to produce afamelanotide. This small change creates a more stable molecule with increased potent biologic effects and a longer half-life (minutes). SCENESSE® increases melanin content of the skin without exposure of the skin to the damaging effects of UVR.

The skin's response to damage from UV radiation - human tanning response

Over 800 patients have been treated with SCENESSE® in more than 20 clinical trials over several indications. Results to date suggest that the drug is well tolerated. In EPP trials, SCENESSE® has been shown to reduce the incidence and severity of phototoxic reactions.

CLINUVEL PHARMACEUTICALS LTD is an ethical pharmaceutical company focused on providing photoprotective care of the skin. CLINUVEL is working closely with global regulatory agencies to develop SCENESSE® as a prescriptive drug. CLINUVEL has been developing and testing SCENESSE® since 2000. Our development is focused on the SAFE and controlled administration of the drug substance.