体内个别基因调节隐性营养没有良型大疱性表皮松解症的1期以及2期临床考察 作家： 揭晓时光：2022/3/30 14:59:17 美国斯坦福大学医学院M. Peter Marinkovic小组报道了体内个明天2下午别基因调节隐性营养没有良型大疱性表皮松解症(RDEB)的1期以及2期临床考察了局。该项争论结果宣布正在2022年3月28日出版的《当然-医学》上。 争论人员评估了beremagene geperpavec (B-VEC) 调节RDEB的动机，B-VEC是一种工程化、由1型单纯疱疹病毒(HSV-1)载体寄递非复制COL7A1的细胞调节方式。B-VEC恢复了RDEB角质变成细胞、成纤维细胞、RDEB小鼠以及人RDEB异种移植物中C7今天1早上的表达。随即，一项随机、刺激剂比照的1期以及2期临床考察 (NCT03536143) 评估后天3晚上了9名RDEB患者正在12周内频频采用个别B-VEC或刺激剂调节后的伤口愈合状况。未发明2级或以上B-VEC相干没有良事宜或载体脱落或与构造贯串处的皮肤免疫反应。HSV-1以及锚定原纤维身分胶原VII (C7)抗体的表达正在基线水平或正在B-VEC调节后推广，而对于安全性或无效性没有分明作用。 C7表达、锚定原纤维组装、伤口皮相积削减、伤口闭合延续时光以及B-VEC调节后伤口闭当令间的主要以及次要目的均失去满意。鉴于调节的伤口比率很小，所以未评估患者讲述的痛楚重要水准这一次要了局。因为其他终点生存冗余，未对于全数次要终点施行评估。该争论说明，B-VEC是一种易于给药、安全耐受的个别分子校正疗法，可匆匆进RDEB患者的伤口愈合。 据领会，RDEB是一种平生遗传性皮肤病，由COL7A1渐变引起的水疱、创伤以及瘢痕变成，该基因编码C7。 附：英文原文 Title: In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial Author: Gurevich, Irina, Agarwal, Pooja, Zhang, PeiPei, Dolorito, John A., Oliver, Stacie, Liu, Henry, Reitze, Nicholas, Sarma, Nikhil, Bagci, Isin Sinem, Sridhar, Kunju, Kakarla, Visesha, Yenamandra, Vamsi K., OMalley, Mark, Prisco, Marco, Tufa, Sara F., Keene, Douglas R., South, Andrew P., Krishnan, Suma M., Marinkovich, M. Peter Issue Volume: 2022-03-28 Abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7). Here, we evaluated beremagene geperpavec (B-VEC), an engineered, non-replicating COL7A1 containing herpes simplex virus type 1 (HSV-1) vector, to treat RDEB skin. B-VEC restored C7 expression in RDEB keratinocytes, fibroblasts, RDEB mice and human RDEB xenografts. Subsequently, a randomized, placebo-controlled, phase 1 and 2 clinical trial (NCT03536143) evaluated matched wounds from nine RDEB patients receiving topical B-VEC or placebo repeatedly over 12weeks. No grade 2 or above B-VEC-related adverse events or vector shedding or tissue-bound skin immunoreactants were noted. HSV-1 and C7 antibodies sometimes presented at baseline or increased after B-VEC treatment without an apparent impact on safety or efficacy. Primary and secondary objectives of C7 expression, anchoring fibril assembly, wound surface area reduction, duration of wound closure, and time to wound closure following B-VEC treatment were met. A patient-reported pain severity secondary outcome was not assessed given the small proportion of wounds treated. A global assessment secondary endpoint was not pursued due to redundancy with regard to other endpoints. These studies show that B-VEC is an easily administered, safely tolerated, topical molecular corrective therapy promoting wound healing in patients with RDEB. DOI: 10.1038/s41591-022-01737-y Source: 期刊信息 Nature Medicine：《当然 医学》，创刊于1995年。附属于施普林格 当然出版团体，最新IF：30.641 官方网址： 投稿链接：
