Effect of Gentamicin Ointment in Patients with Nagashima-type Palmoplantar Keratosis: A Double-blind Vehicle-controlled Study
DOI:
https://doi.org/10.2340/00015555-3760Keywords:
Nagashima-type palmoplantar keratosis, readthrough, gentamicinAbstract
Gentamicin ointment has potential in the treatment of Nagashima-type palmoplantar keratosis. However, there is a lack of reliable study data. The aim of this study was to perform a prospective, randomized, double-blinded, contralateral, vehicle-controlled clinical trial. A total of 20 subjects diagnosed with Nagashima-type palmoplantar keratosis by genetic test, who carried nonsense mutations, enrolled in the 30-day study. Gentamicin ointment was applied to the hand and foot on one side of the body, and vehicle ointment was applied to the hand and foot on the other side. The choice of hand and foot in each subject was randomly allocated. The severity of the patient’s skin lesions and quality of life were assessed by a blinded evaluator, using the Dermatology Life Quality Index, visual analogue scale scores and digital photography. Gentamicin ointment treatment resulted in a significant improvement in symptoms of hyperkeratosis and foul smell compared with vehicle. No difference was found in the effect on erythema between gentamicin and vehicle. In conclusion, gentamicin ointment demonstrated positive responses and good tolerance in treating Nagashima-type palmoplantar keratosis caused by nonsense mutations.
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Kubo A, Shiohama A, Sasaki T, Nakabayashi K, Kawasaki H, Atsugi T, et al. Mutations in SERPINB7, encoding a member of the serine protease inhibitor superfamily, cause Nagashima-type palmoplantar keratosis. Am J Hum Genet 2013; 93: 945-956.
DOI: https://doi.org/10.1016/j.ajhg.2013.09.015
Nakamizo S, Katoh N, Miyachi Y, Kabashima K. Atypical nail dystrophy in a possible case of Nagashima-type palmoplantar keratosis. J Dermatol 2012; 39: 470-471.
DOI: https://doi.org/10.1111/j.1346-8138.2011.01326.x
Nonomura Y, Otsuka A, Miyachi Y, Kabashima K. Suspected Nagashima-type palmoplantar keratosis with atypical hyperkeratotic lesions on the ears. Eur J Dermatol 2012; 22: 392-393.
DOI: https://doi.org/10.1684/ejd.2012.1676
Kabashima K, Sakabe J, Yamada Y, Tokura Y. "Nagashima-type" keratosis as a novel entity in the palmoplantar keratoderma category. Arch Dermatol 2008; 144: 375-379.
DOI: https://doi.org/10.1001/archderm.144.3.375
Gerber PA, Hevezi P, Buhren BA, Martinez C, Schrumpf H, Gasis M, et al. Systematic identification and characterization of novel human skin-associated genes encoding membrane and secreted proteins. PLoS One 2013; 8: e63949.
DOI: https://doi.org/10.1371/journal.pone.0063949
Mizuno O, Nomura T, Suzuki S, Takeda M, Ohguchi Y, Fujita Y, et al. Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis. Br J Dermatol 2014; 171: 847-853.
DOI: https://doi.org/10.1111/bjd.13076
Yin J, Xu G, Wang H, Zhao J, Duo L, Cao X, et al. New and recurrent SERPINB7 mutations in seven Chinese patients with Nagashima-type palmoplantar keratosis. J Invest Dermatol 2014; 134: 2269-2272.
DOI: https://doi.org/10.1038/jid.2014.80
Sakabe JI, Kabashima K, Sugita K, Tokura Y. Possible involvement of T lymphocytes in the pathogenesis of Nagashima-type keratosis palmoplantaris. Clin Exp Dermatol 2009; 34: e282-e284.
DOI: https://doi.org/10.1111/j.1365-2230.2008.03202.x
Woodley DT, Cogan J, Hou Y, Lyu C, Marinkovich MP, Keene D, et al. Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients. J Clin Invest 2017; 127: 3028-3038.
DOI: https://doi.org/10.1172/JCI92707
Ohguchi Y, Nomura T, Suzuki S, Takeda M, Miyauchi T, Mizuno O, et al. Gentamicin-induced readthrough and nonsense-mediated mRNA decay of SERPINB7 nonsense mutant transcripts. J Invest Dermatol 2018; 138: 836-843.
DOI: https://doi.org/10.1016/j.jid.2017.10.014
Keeling KM, Xue X, Gunn G, Bedwell DM. Therapeutics based on stop codon readthrough. Annu Rev Genomics Hum Genet 2014; 15: 371-394.
DOI: https://doi.org/10.1146/annurev-genom-091212-153527
Bidou L, Allamand V, Rousset JP, Namy O. Sense from nonsense: therapies for premature stop codon diseases. Trends Mol Med 2012; 18: 679-688.
DOI: https://doi.org/10.1016/j.molmed.2012.09.008
Linde L, Kerem B. Introducing sense into nonsense in treatments of human genetic diseases. Trends Genet 2008; 24: 552-563.
DOI: https://doi.org/10.1016/j.tig.2008.08.010
Li M, Liu Q, Liu J, Cheng R, Zhang H, Xue H, et al. Mutations analysis in filaggrin gene in northern China patients with atopic dermatitis. J Eur Acad Dermatol Venereol 2013; 27: 169-174.
DOI: https://doi.org/10.1111/j.1468-3083.2011.04435.x
Bedwell DM, Kaenjak A, Benos DJ, Bebok Z, Bubien JK, Hong J, et al. Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line. Nat Med 1997; 3: 1280-1284.
DOI: https://doi.org/10.1038/nm1197-1280
Wagner KR, Hamed S, Hadley DW, Gropman AL, Burstein AH, Escolar DM, et al. Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations. Ann Neurol 2001; 49: 706-711.
DOI: https://doi.org/10.1002/ana.1023
Lincoln V, Cogan J, Hou Y, Hirsch M, Hao M, Alexeev V, et al. Gentamicin induces LAMB3 nonsense mutation readthrough and restores functional laminin 332 in junctional epidermolysis bullosa. Proc Natl Acad Sci U S A 2018; 115: E6536-E6545.
DOI: https://doi.org/10.1073/pnas.1803154115
Cogan J, Weinstein J, Wang X, Hou Y, Martin S, South AP, et al. Aminoglycosides restore full-length type VII collagen by overcoming premature termination codons: therapeutic implications for dystrophic epidermolysis bullosa. Mol Ther 2014; 22: 1741-1752.
DOI: https://doi.org/10.1038/mt.2014.140
Kellermayer R, Szigeti R, Keeling KM, Bedekovics T, Bedwell DM. Aminoglycosides as potential pharmacogenetic agents in the treatment of Hailey-Hailey disease. J Invest Dermatol 2006; 126: 229-231.
DOI: https://doi.org/10.1038/sj.jid.5700031
Keeling KM, Xue X, Gunn G, Bedwell DM. Therapeutics based on stop codon readthrough. Annu Rev Genomics Hum Genet 2014; 15: 371-394.
DOI: https://doi.org/10.1146/annurev-genom-091212-153527
Atanasova VS, Jiang Q, Prisco M, Gruber C, Piñón Hofbauer J, Chen M, et al. Amlexanox enhances premature termination codon read-through in COL7A1 and expression of full length type VII collagen: potential therapy for recessive dystrophic epidermolysis bullosa. J Invest Dermatol 2017; 137: 1842-1849.
DOI: https://doi.org/10.1016/j.jid.2017.05.011
Banning A, Schiff M, Tikkanen R. Amlexanox provides a potential therapy for nonsense mutations in the lysosomal storage disorder aspartylglucosaminuria. Biochim Biophys Acta Mol Basis Dis 2018; 1864: 668-675.
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Copyright (c) 2021 Yue Li, Xia Yu, Chaolan Pan, Yumeng Wang, Jianwen Han, Zhirong Yao, Ming Li
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