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Randomized, split-body, single-blinded clinical trial of topical broccoli sprout extract: Assessing the feasibility of its use in keratin-based disorders - 18/04/17

Doi : 10.1016/j.jaad.2016.10.009 
Michelle L. Kerns, MD a, Lark Guss, MD b, Jed Fahey, PhD c, Bernard Cohen, MD b, d, Jill M.C. Hakim, BS a, Sarah Sung, MD b, Rosemary G. Lu, ScM a, Pierre A. Coulombe, PhD a, b, e, f,
a Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 
b Department of Dermatology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 
c Department of Clinical Pharmacology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 
d Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland 
e Department of Biological Chemistry, School of Medicine, Johns Hopkins University, Baltimore, Maryland 
f Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 

Reprint requests: Pierre A. Coulombe, PhD, Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 N Wolfe St, Room W8041, Baltimore, MD 21205.Department of Biochemistry and Molecular BiologyBloomberg School of Public HealthJohns Hopkins University615 N Wolfe St, Room W8041BaltimoreMD21205

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.

Il testo completo di questo articolo è disponibile in PDF.

Key words : broccoli sprout extract, epidermolysis bullosa simplex, keratin, nuclear factor (erythroid-derived 2)-like 2, sulforaphane

Abbreviations used : BSE, EBS, K, NRF2


Mappa


 Drs Kerns and Guss contributed equally to this work.
 Supported by internal funds at Johns Hopkins University.
 Conflicts of interest: None declared.


© 2016  American Academy of Dermatology, Inc.. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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