Michelle L Kerns1, Lark Guss2, Jed Fahey3, Bernard Cohen4, Jill M C Hakim1, Sarah Sung2, Rosemary G Lu1, Pierre A Coulombe5. 1. Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland. 2. Department of Dermatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. 3. Department of Clinical Pharmacology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. 4. Department of Dermatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland. 5. Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; Department of Dermatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland. Electronic address: coulombe@jhu.edu.
Abstract
BACKGROUND: Epidermolysis bullosa simplex is a skin-blistering disorder caused by mutations in keratin (K)14 or K5. Treatment with nuclear factor (erythroid-derived 2)-like 2 inducer sulforaphane ameliorated skin blistering in Krt14-null mice, correlating with induction of K17. To be therapeutically useful for epidermolysis bullosa simplex, topical broccoli sprout extract (BSE), enriched for sulforaphane, would ideally induce the expression of homologous keratins (eg, K6, K17, K16) in the basal layer of human epidermis without impacting expression of defective keratins (K5/K14). OBJECTIVE: The purpose of this 1-week, randomized, split-body, single-blinded, placebo-controlled trial was to assess the impact of BSE on keratin expression. METHODS: Five subjects (34-71 years old) applied BSE (500 nmol of sulforaphane/mL) or vehicle alone to the inner aspect of the arm daily. Expression of keratin, nuclear factor (erythroid-derived 2)-like 2, and other markers was assessed using reverse transcription-polymerase chain reaction and indirect immunofluorescence. RESULTS: One subject (age 71 years) was excluded a posteriori because of poor tissue quality. Topical BSE activated nuclear factor (erythroid-derived 2)-like 2 and up-regulated K17 in the epidermis of all subjects, had variable effects on K16 and K6 expression, and did not alter expression of K14 or K5. LIMITATIONS: Small sample size is a limitation. CONCLUSION:BSE represents an attractive therapeutic candidate for K14-associated epidermolysis bullosa simplex.
RCT Entities:
BACKGROUND: Epidermolysis bullosa simplex is a skin-blistering disorder caused by mutations in keratin (K)14 or K5. Treatment with nuclear factor (erythroid-derived 2)-like 2 inducer sulforaphane ameliorated skin blistering in Krt14-null mice, correlating with induction of K17. To be therapeutically useful for epidermolysis bullosa simplex, topical broccoli sprout extract (BSE), enriched for sulforaphane, would ideally induce the expression of homologous keratins (eg, K6, K17, K16) in the basal layer of human epidermis without impacting expression of defective keratins (K5/K14). OBJECTIVE: The purpose of this 1-week, randomized, split-body, single-blinded, placebo-controlled trial was to assess the impact of BSE on keratin expression. METHODS: Five subjects (34-71 years old) applied BSE (500 nmol of sulforaphane/mL) or vehicle alone to the inner aspect of the arm daily. Expression of keratin, nuclear factor (erythroid-derived 2)-like 2, and other markers was assessed using reverse transcription-polymerase chain reaction and indirect immunofluorescence. RESULTS: One subject (age 71 years) was excluded a posteriori because of poor tissue quality. Topical BSE activated nuclear factor (erythroid-derived 2)-like 2 and up-regulated K17 in the epidermis of all subjects, had variable effects on K16 and K6 expression, and did not alter expression of K14 or K5. LIMITATIONS: Small sample size is a limitation. CONCLUSION: BSE represents an attractive therapeutic candidate for K14-associated epidermolysis bullosa simplex.
Authors: Michelle L Kerns; Daryle DePianto; Albena T Dinkova-Kostova; Paul Talalay; Pierre A Coulombe Journal: Proc Natl Acad Sci U S A Date: 2007-08-27 Impact factor: 11.205
Authors: Jed W Fahey; W David Holtzclaw; Scott L Wehage; Kristina L Wade; Katherine K Stephenson; Paul Talalay Journal: PLoS One Date: 2015-11-02 Impact factor: 3.240
Authors: Tom Clifford; Jarred P Acton; Stuart P Cocksedge; Kelly A Bowden Davies; Stephen J Bailey Journal: Mol Biol Rep Date: 2021-01-30 Impact factor: 2.316
Authors: Thomas Kocher; Patricia Peking; Alfred Klausegger; Eva Maria Murauer; Josefina Piñón Hofbauer; Verena Wally; Thomas Lettner; Stefan Hainzl; Michael Ablinger; Johann Wolfgang Bauer; Julia Reichelt; Ulrich Koller Journal: Mol Ther Date: 2017-08-24 Impact factor: 11.454
Authors: Michael Ablinger; Thomas K Felder; Monika Wimmer; Roland Zauner; Peter Hofbauer; Thomas Lettner; Martin Wolkersdorfer; Florian B Lagler; Anja Diem; Johann W Bauer; Verena Wally Journal: Orphanet J Rare Dis Date: 2018-11-01 Impact factor: 4.123
Authors: Michelle L Kerns; Robert J Miller; Momina Mazhar; Angel S Byrd; Nathan K Archer; Bret L Pinkser; Lance Lew; Carly A Dillen; Ruizhi Wang; Lloyd S Miller; Anna L Chien; Sewon Kang Journal: JCI Insight Date: 2020-10-15