In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial
| العنوان: | In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial |
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| المؤلفون: | Irina Gurevich, Pooja Agarwal, PeiPei Zhang, John A. Dolorito, Stacie Oliver, Henry Liu, Nicholas Reitze, Nikhil Sarma, Isin Sinem Bagci, Kunju Sridhar, Visesha Kakarla, Vamsi K. Yenamandra, Mark O’Malley, Marco Prisco, Sara F. Tufa, Douglas R. Keene, Andrew P. South, Suma M. Krishnan, M. Peter Marinkovich |
| المصدر: | Nature Medicine. 28:780-788 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | integumentary system, General Medicine, General Biochemistry, Genetics and Molecular Biology |
| الوصف: | 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 12 weeks. 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. |
| تدمد: | 1546-170X 1078-8956 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::ce9c26f71edbe1ea4feaf5906f51c6c4 https://doi.org/10.1038/s41591-022-01737-y |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........ce9c26f71edbe1ea4feaf5906f51c6c4 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1546170X 10788956 |
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