Innovations in the Treatment of Dystrophic Epidermolysis Bullosa (DEB): Current Landscape and Prospects

References

• Bardhan A, Bruckner-Tuderman L, Chapple IL, et al. Epidermolysis bullosa. Nat Rev Dis Primers. 2020;6(1):78. doi:10.1038/s41572-020-0210-0
   PubMed Web of Science ®Google Scholar
• Has C, Bauer JW, Bodemer C, et al. Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility. Br J Dermatol. 2020;183(4):614–627. doi:10.1111/bjd.18921
   PubMed Web of Science ®Google Scholar
• Petrof G, Papanikolaou M, Martinez AE, et al. The epidemiology of epidermolysis bullosa in England and Wales: data from the national epidermolysis bullosa database. Br J Dermatol. 2022;186(5):843–848. doi:10.1111/bjd.20958
   PubMed Web of Science ®Google Scholar
• Nyström A, Bornert O, Kühl T, et al. Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa. Proc Natl Acad Sci U S A. 2018;115(4):E705–E714. doi:10.1073/pnas.1709111115
   PubMed Web of Science ®Google Scholar
• Tartaglia G, Cao Q, Padron ZM, South AP. Impaired wound healing, fibrosis, and cancer: the paradigm of recessive dystrophic epidermolysis bullosa. Int J Mol Sci. 2021;22(10):5104. doi:10.3390/ijms22105104
   PubMed Web of Science ®Google Scholar
• Fine JD, Johnson LB, Weiner M, Li KP, Suchindran C. Epidermolysis bullosa and the risk of life-threatening cancers: the national EB registry experience, 1986–2006. J Am Acad Dermatol. 2009;60(2):203–211. doi:10.1016/j.jaad.2008.09.035
   PubMed Web of Science ®Google Scholar
• Feinstein JA, Bruckner AL, Chastek B, Anderson A, Roman J. Clinical characteristics, healthcare use, and annual costs among patients with dystrophic epidermolysis bullosa. Orphanet J Rare Dis. 2022;17(1):367. doi:10.1186/s13023-022-02509-0
   PubMed Web of Science ®Google Scholar
• Angelis A, Mellerio JE, Kanavos P. Understanding the socioeconomic costs of dystrophic epidermolysis bullosa in Europe: a costing and health-related quality of life study. Orphanet J Rare Dis. 2022;17(1):346. doi:10.1186/s13023-022-02419-1
   PubMed Web of Science ®Google Scholar
• Chen M, O’Toole EA, Muellenhoff M, Medina E, Kasahara N, Woodley DT. Development and characterization of a recombinant truncated type VII collagen “minigene”. Implication for gene therapy of dystrophic epidermolysis bullosa. J Biol Chem. 2000;275(32):24429–24435. doi:10.1074/jbc.M003440200
   PubMed Web of Science ®Google Scholar
• Chen M, Kasahara N, Keene DR, et al. Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa. Nat Genet. 2002;32(4):670–675. doi:10.1038/ng1041
   PubMed Web of Science ®Google Scholar
• Baldeschi C, Gache Y, Rattenholl A, et al. Genetic correction of canine dystrophic epidermolysis bullosa mediated by retroviral vectors. Hum Mol Genet. 2003;12(15):1897–1905. doi:10.1093/hmg/ddg200
   PubMed Web of Science ®Google Scholar
• Goto M, Sawamura D, Ito K, et al. Fibroblasts show more potential as target cells than keratinocytes in COL7A1 gene therapy of dystrophic epidermolysis bullosa. J Invest Dermatol. 2006;126(4):766–772. doi:10.1038/sj.jid.5700117
   PubMed Web of Science ®Google Scholar
• Ortiz-Urda S, Lin Q, Green CL, Keene DR, Marinkovich MP, Khavari PA. Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue. J Clin Invest. 2003;111(2):251–255. doi:10.1172/JCI200317193
   PubMed Web of Science ®Google Scholar
• Siprashvili Z, Nguyen NT, Bezchinsky MY, Marinkovich MP, Lane AT, Khavari PA. Long-term type VII collagen restoration to human epidermolysis bullosa skin tissue. Hum Gene Ther. 2010;21(10):1299–1310. doi:10.1089/hum.2010.023
   PubMed Web of Science ®Google Scholar
• Titeux M, Pendaries V, Zanta-Boussif MA, et al. SIN retroviral vectors expressing COL7A1 under human promoters for ex vivo gene therapy of recessive dystrophic epidermolysis bullosa. Mol Ther. 2010;18(8):1509–1518 doi:10.1038/mt.2010.91.
   PubMed Web of Science ®Google Scholar
• Woodley DT, Krueger GG, Jorgensen CM, et al. Normal and gene-corrected dystrophic epidermolysis bullosa fibroblasts alone can produce type VII collagen at the basement membrane zone. J Invest Dermatol. 2003;121(5):1021–1028. doi:10.1046/j.1523-1747.2003.12571.x
   PubMed Web of Science ®Google Scholar
• Siprashvili Z, Nguyen NT, Gorell ES, et al. Safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with recessive dystrophic epidermolysis bullosa. JAMA. 2016;316(17):1808–1817 doi:10.1001/jama.2016.15588.
   PubMed Web of Science ®Google Scholar
• Eichstadt S, Barriga M, Ponakala A, et al. Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa. JCI Insight. 2019;4(19):e130554 doi:10.1172/jci.insight.130554.
   PubMed Web of Science ®Google Scholar
• So JY, Nazaroff J, Iwummadu CV, et al. Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa. Orphanet J Rare Dis. 2022;17(1):377. doi:10.1186/s13023-022-02546-9
   PubMed Web of Science ®Google Scholar
• Lwin SM, Syed F, Di WL, et al. Safety and early efficacy outcomes for lentiviral fibroblast gene therapy in recessive dystrophic epidermolysis bullosa. JCI Insight. 2019;4(11):e126243. doi:10.1172/jci.insight.126243
   PubMed Web of Science ®Google Scholar
• Marinkovich M, Lane A, Sridhar K, Keene DR, Malyala A, Maslowski J. 591 A phase 1/2 study of genetically-corrected, collagen VII expressing autologous human dermal fibroblasts injected into the skin of patients with recessive dystrophic epidermolysis bullosa (RDEB). J Invest Dermatol. 2018;138(5):S100. doi:10.1016/j.jid.2018.03.599
   Web of Science ®Google Scholar
• Gurevich I, Agarwal P, Zhang P, et al. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022;28(4):780–788. doi:10.1038/s41591-022-01737-y
   PubMed Web of Science ®Google Scholar
• Guide SV, Gonzalez ME, Bağcı IS, et al. Trial of beremagene geperpavec (B-VEC) for dystrophic epidermolysis bullosa. N Engl J Med. 2022;387(24):2211–2219. doi:10.1056/NEJMoa2206663
   PubMed Web of Science ®Google Scholar
• Osborn MJ, Starker CG, McElroy AN, et al. Talen-based gene correction for epidermolysis bullosa. Mol Ther. 2013;21(6):1151–1159. doi:10.1038/mt.2013.56
   PubMed Web of Science ®Google Scholar
• Izmiryan A, Ganier C, Bovolenta M, Schmitt A, Mavilio F, Hovnanian A. Ex vivo COL7A1 correction for recessive dystrophic epidermolysis bullosa using CRISPR/Cas9 and homology-directed repair. Mol Ther Nucleic Acids. 2018;12:554–567 doi:10.1016/j.omtn.2018.06.008.
   PubMedGoogle Scholar
• Jacków J, Guo Z, Hansen C, et al. CRISPR/Cas9-based targeted genome editing for correction of recessive dystrophic epidermolysis bullosa using IPS cells. Proc Natl Acad Sci U S A. 2019;116(52):26846–26852 doi:10.1073/pnas.1907081116.
   PubMed Web of Science ®Google Scholar
• Shinkuma S, Guo Z, Christiano AM. Site-specific genome editing for correction of induced pluripotent stem cells derived from dominant dystrophic epidermolysis bullosa. Proc Natl Acad Sci U S A. 2016;113(20):5676–5681. doi:10.1073/pnas.1512028113
   PubMed Web of Science ®Google Scholar
• Neumayer G, Torkelson JL, Li S, et al. A scalable, GMP-compatible, autologous organotypic cell therapy for dystrophic epidermolysis bullosa. bioRxiv. 2023. doi:10.1101/2023.02.28.529447
   PubMedGoogle Scholar
• Gaudelli NM, Komor AC, Rees HA, et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature. 2017;551(7681):464–471. doi:10.1038/nature24644
   PubMed Web of Science ®Google Scholar
• Rees HA, Liu DR. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat Rev Genet. 2018;19(12):770–788. doi:10.1038/s41576-018-0059-1
   PubMed Web of Science ®Google Scholar
• Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016;533(7603):420–424. doi:10.1038/nature17946
   PubMed Web of Science ®Google Scholar
• Osborn MJ, Newby GA, McElroy AN, et al. Base editor correction of COL7A1 in recessive dystrophic epidermolysis bullosa patient-derived fibroblasts and IPSCs. J Invest Dermatol. 2020;140(2):338–347.e5. doi:10.1016/j.jid.2019.07.701
   PubMed Web of Science ®Google Scholar
• Sheriff A, Guri I, Zebrowska P, et al. ABE8e adenine base editor precisely and efficiently corrects a recurrent COL7A1 nonsense mutation. Sci Rep. 2022;12(1):19643. doi:10.1038/s41598-022-24184-8
   PubMed Web of Science ®Google Scholar
• Naso G, Gkazi SA, Georgiadis C, et al. Cytosine deaminase base editing to restore COL7A1 in dystrophic epidermolysis bullosa human: murine skin model. JID Innovations. 2023;3(3):100191. doi:10.1016/j.xjidi.2023.100191
   PubMedGoogle Scholar
• Anzalone AV, Randolph PB, Davis JR, et al. Search-and-replace genome editing without double-strand breaks or donor DNA. Nature. 2019;576(7785):149–157. doi:10.1038/s41586-019-1711-4
   PubMed Web of Science ®Google Scholar
• Hong SA, Kim SE, Lee AY, et al. Therapeutic base editing and prime editing of COL7A1 mutations in recessive dystrophic epidermolysis bullosa. Mol Ther. 2022;30(8):2664–2679. doi:10.1016/j.ymthe.2022.06.005
   PubMed Web of Science ®Google Scholar
• Bauer JW, Murauer EM, Wally V, Koller U. RNA trans-splicing for genodermatoses. Methods Mol Biol. 2013;961:441–455 doi:10.1007/978-1-62703-227-8_30.
   PubMedGoogle Scholar
• Bornert O, Peking P, Bremer J, et al. RNA-based therapies for genodermatoses. Exp Dermatol. 2017;26(1):3–10. doi:10.1111/exd.13141
   PubMed Web of Science ®Google Scholar
• Murauer EM, Gache Y, Gratz IK, et al. Functional correction of type VII collagen expression in dystrophic epidermolysis bullosa. J Invest Dermatol. 2011;131(1):74–83. doi:10.1038/jid.2010.249
   PubMed Web of Science ®Google Scholar
• Mayr E, Ablinger M, Lettner T, et al. 5’RNA trans-splicing repair of COL7A1 mutant transcripts in epidermolysis bullosa. Int J Mol Sci. 2022;23(3):1732. doi:10.3390/ijms23031732
   PubMed Web of Science ®Google Scholar
• Murauer EM, Koller U, Hainzl S, Wally V, Bauer JW. A reporter-based screen to identify potent 3’ trans-splicing molecules for endogenous RNA repair. Hum Gene Ther Methods. 2013;24(1):19–27. doi:10.1089/hgtb.2012.180
   PubMed Web of Science ®Google Scholar
• Bremer J, Bornert O, Nyström A, et al. Antisense oligonucleotide-mediated exon skipping as a systemic therapeutic approach for recessive dystrophic epidermolysis bullosa. Mol Ther Nucleic Acids. 2016;5(10):e379. doi:10.1038/mtna.2016.87
   PubMedGoogle Scholar
• Bremer J, van den Akker PC. Therapies for epidermolysis bullosa: delivery is key. Br J Dermatol. 2019;180(1):17–19. doi:10.1111/bjd.17324
   PubMed Web of Science ®Google Scholar
• Liemberger B, Bischof J, Ablinger M, et al. COL7A1 editing via RNA trans-splicing in RDEB-derived skin equivalents. Int J Mol Sci. 2023;24(5):4341. doi:10.3390/ijms24054341
   PubMed Web of Science ®Google Scholar
• Tarn WY, Cheng Y, Ko SH, Huang LM. Antisense oligonucleotide-based therapy of viral infections. Pharmaceutics. 2021;13(12):2015. doi:10.3390/pharmaceutics13122015
   PubMed Web of Science ®Google Scholar
• Rodrigues M, Yokota T. An overview of recent advances and clinical applications of exon skipping and splice modulation for muscular dystrophy and various genetic diseases. Methods Mol Biol. 2018;1828:31–55 doi:10.1007/978-1-4939-8651-4_2.
   PubMedGoogle Scholar
• Goto M, Sawamura D, Nishie W, et al. Targeted skipping of a single exon harboring a premature termination codon mutation: implications and potential for gene correction therapy for selective dystrophic epidermolysis bullosa patients. J Invest Dermatol. 2006;126(12):2614–2620. doi:10.1038/sj.jid.5700435
   PubMed Web of Science ®Google Scholar
• Bornert O, Hogervorst M, Nauroy P, et al. QR-313, an antisense oligonucleotide, shows therapeutic efficacy for treatment of dominant and recessive dystrophic epidermolysis bullosa: a preclinical study. J Invest Dermatol. 2021;141(4):883–893.e6. doi:10.1016/j.jid.2020.08.018
   PubMed Web of Science ®Google Scholar
• Ham KA, Aung-Htut MT, Fletcher S, Wilton SD. Nonsequential splicing events alter antisense-mediated exon skipping outcome in COL7A1. Int J Mol Sci. 2020;21(20):7705. doi:10.3390/ijms21207705
   PubMed Web of Science ®Google Scholar
• Turczynski S, Titeux M, Tonasso L, Décha A, Ishida-Yamamoto A, Hovnanian A. Targeted exon skipping restores type VII collagen expression and anchoring fibril formation in an in vivo RDEB model. J Invest Dermatol. 2016;136(12):2387–2395. doi:10.1016/j.jid.2016.07.029
   PubMed Web of Science ®Google Scholar
• Marinkovich MP, Sridhar K, Karkala V, Y VK. 306 Topical QR-313, an antisense oligonucleotide, in the treatment of dystrophic epidermolysis bullosa. J Invest Dermatol. 2020;140(7):S37 doi:10.1016/j.jid.2020.03.312.
   Web of Science ®Google Scholar
• Pendaries V, Gasc G, Titeux M, Tonasso L, Mejía JE, Hovnanian A. SiRNA-mediated allele-specific inhibition of mutant type VII collagen in dominant dystrophic epidermolysis bullosa. J Invest Dermatol. 2012;132(6):1741–1743. doi:10.1038/jid.2012.11
   PubMed Web of Science ®Google Scholar
• Bornert O, Kühl T, Bremer J, van den Akker PC, Pasmooij AM, Nyström A. Analysis of the functional consequences of targeted exon deletion in COL7A1 reveals prospects for dystrophic epidermolysis bullosa therapy. Mol Ther. 2016;24(7):1302–1311. doi:10.1038/mt.2016.92
   PubMed Web of Science ®Google Scholar
• Jonkman MF, Scheffer H, Stulp R, et al. Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion. Cell. 1997;88(4):543–551. doi:10.1016/S0092-8674(00)81894-2
   PubMed Web of Science ®Google Scholar
• Almaani N, Nagy N, Liu L, et al. Revertant mosaicism in recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2010;130(7):1937–1940. doi:10.1038/jid.2010.64
   PubMed Web of Science ®Google Scholar
• Twaroski K, Eide C, Riddle MJ, et al. Revertant mosaic fibroblasts in recessive dystrophic epidermolysis bullosa. Br J Dermatol. 2019;181(6):1247–1253. doi:10.1111/bjd.17943
   PubMed Web of Science ®Google Scholar
• Shinkuma S, Sawamura D, Fujita Y, et al. Long-term follow-up of cultured epidermal autograft in a patient with recessive dystrophic epidermolysis bullosa. Acta Derm Venereol. 2014;94(1):98–99. doi:10.2340/00015555-1592
   PubMed Web of Science ®Google Scholar
• Mochizuki R, Oka Y, Hashimoto S, et al. A case of recessive dystrophic epidermolysis bullosa treated with a cultured epidermal autograft. J Dermatol. 2021;48(4):e165–e166. doi:10.1111/1346-8138.15774
   PubMed Web of Science ®Google Scholar
• Bidou L, Allamand V, Rousset JP, Namy O. Sense from nonsense: therapies for premature stop codon diseases. Trends Mol Med. 2012;18(11):679–688. doi:10.1016/j.molmed.2012.09.008
   PubMed Web of Science ®Google Scholar
• Cogan J, Weinstein J, Wang X, et al. Aminoglycosides restore full-length type VII collagen by overcoming premature termination codons: therapeutic implications for dystrophic epidermolysis bullosa. Mol Ther. 2014;22(10):1741–1752. doi:10.1038/mt.2014.140
   PubMed Web of Science ®Google Scholar
• Woodley DT, Cogan J, Hou Y, et al. Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients. J Clin Invest. 2017;127(8):3028–3038. doi:10.1172/JCI92707
   PubMed Web of Science ®Google Scholar
• Woodley D, Kwong A, Cogan J, Hou Y. 1021 Intravenous gentamicin therapy for recessive dystrophic epidermolysis bullosa patients harboring nonsense mutations. J Invest Dermatol. 2019;139(5):S176. doi:10.1016/j.jid.2019.03.1097
   Web of Science ®Google Scholar
• Mosallaei D, Hao M, Antaya RJ, et al. Molecular and clinical outcomes after intravenous gentamicin treatment for patients with junctional epidermolysis bullosa caused by nonsense variants. JAMA Dermatol. 2022;158(4):366–374. doi:10.1001/jamadermatol.2021.5992
   PubMed Web of Science ®Google Scholar
• Martínez-Santamaría L, Maseda R, de Arriba MD, et al. Evaluation of systemic gentamicin as translational readthrough therapy for a patient with epidermolysis bullosa simplex with muscular dystrophy owing to PLEC1 pathogenic nonsense variants. JAMA Dermatol. 2022;158(4):439–443. doi:10.1001/jamadermatol.2022.0112
   PubMed Web of Science ®Google Scholar
• Friesen WJ, Johnson B, Sierra J, et al. The minor gentamicin complex component, X2, is a potent premature stop codon readthrough molecule with therapeutic potential. PLoS One. 2018;13(10):e0206158. doi:10.1371/journal.pone.0206158
   PubMed Web of Science ®Google Scholar
• McElroy SP, Nomura T, Torrie LS, et al. A lack of premature termination codon read-through efficacy of PTC124 (Ataluren) in a diverse array of reporter assays. PLoS Biol. 2013;11(6):e1001593. doi:10.1371/journal.pbio.1001593
   PubMed Web of Science ®Google Scholar
• Atanasova VS, Jiang Q, Prisco 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(9):1842–1849. doi:10.1016/j.jid.2017.05.011
   PubMed Web of Science ®Google Scholar
• Wong T, Gammon L, Liu L, et al. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2008;128(9):2179–2189. doi:10.1038/jid.2008.78
   PubMed Web of Science ®Google Scholar
• Venugopal SS, Yan W, Frew JW, et al. A phase II randomized vehicle-controlled trial of intradermal allogeneic fibroblasts for recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 2013;69(6):898–908.e7. doi:10.1016/j.jaad.2013.08.014
   PubMed Web of Science ®Google Scholar
• Petrof G, Martinez-Queipo M, Mellerio JE, Kemp P, McGrath JA. Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial. Br J Dermatol. 2013;169(5):1025–1033. doi:10.1111/bjd.12599
   PubMed Web of Science ®Google Scholar
• Moravvej H, Abdollahimajd F, Naseh MH, et al. Cultured allogeneic fibroblast injection vs. fibroblasts cultured on amniotic membrane scaffold for dystrophic epidermolysis bullosa treatment. Br J Dermatol. 2018;179(1):72–79. doi:10.1111/bjd.16338
   PubMed Web of Science ®Google Scholar
• Nagy N, Almaani N, Tanaka A, et al. HB-EGF induces COL7A1 expression in keratinocytes and fibroblasts: possible mechanism underlying allogeneic fibroblast therapy in recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2011;131(8):1771–1774. doi:10.1038/jid.2011.85
   PubMed Web of Science ®Google Scholar
• Tolar J, Ishida-Yamamoto A, Riddle M, et al. Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells. Blood. 2009;113(5):1167–1174. doi:10.1182/blood-2008-06-161299
   PubMed Web of Science ®Google Scholar
• Chino T, Tamai K, Yamazaki T, et al. Bone marrow cell transfer into fetal circulation can ameliorate genetic skin diseases by providing fibroblasts to the skin and inducing immune tolerance. Am J Pathol. 2008;173(3):803–814. doi:10.2353/ajpath.2008.070977
   PubMed Web of Science ®Google Scholar
• Wagner JE, Ishida-Yamamoto A, McGrath JA, et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010;363(7):629–639. doi:10.1056/NEJMoa0910501
   PubMed Web of Science ®Google Scholar
• Uitto J, Bruckner-Tuderman L, McGrath JA, Riedl R, Robinson C. EB2017-progress in epidermolysis bullosa research toward treatment and cure. J Invest Dermatol. 2018;138(5):1010–1016. doi:10.1016/j.jid.2017.12.016
   PubMed Web of Science ®Google Scholar
• Geyer MB, Radhakrishnan K, Giller R, et al. Reduced toxicity conditioning and allogeneic hematopoietic progenitor cell transplantation for recessive dystrophic epidermolysis bullosa. J Pediatr. 2015;167(3):765–769.e1. doi:10.1016/j.jpeds.2015.05.051
   PubMed Web of Science ®Google Scholar
• Tolar J, Wagner JE. Allogeneic blood and bone marrow cells for the treatment of severe epidermolysis bullosa: repair of the extracellular matrix. Lancet. 2013;382(9899):1214–1223. doi:10.1016/S0140-6736(13)61897-8
   PubMed Web of Science ®Google Scholar
• Ebens CL, McGrath JA, Riedl JA, et al. Immune tolerance of allogeneic haematopoietic cell transplantation supports donor epidermal grafting of recessive dystrophic epidermolysis bullosa chronic wounds. Br J Dermatol. 2021;184(6):1161–1169. doi:10.1111/bjd.19503
   PubMed Web of Science ®Google Scholar
• Riedl J, Popp C, Eide C, Ebens C, Tolar J. Mesenchymal stromal cells in wound healing applications: role of the secretome, targeted delivery and impact on recessive dystrophic epidermolysis bullosa treatment. Cytotherapy. 2021;23(11):961–973. doi:10.1016/j.jcyt.2021.06.004
   PubMed Web of Science ®Google Scholar
• Golchin A, Farahany TZ, Khojasteh A, Soleimanifar F, Ardeshirylajimi A. The clinical trials of mesenchymal stem cell therapy in skin diseases: an update and concise review. Curr Stem Cell Res Ther. 2019;14(1):22–33. doi:10.2174/1574888X13666180913123424
   PubMed Web of Science ®Google Scholar
• Jo H, Brito S, Kwak BM, Park S, Lee MG, Bin BH. Applications of mesenchymal stem cells in skin regeneration and rejuvenation. Int J Mol Sci. 2021;22(5):2410. doi:10.3390/ijms22052410
   PubMed Web of Science ®Google Scholar
• McBride JD, Rodriguez-Menocal L, Candanedo A, Guzman W, Garcia-Contreras M, Badiavas EV. Dual mechanism of type VII collagen transfer by bone marrow mesenchymal stem cell extracellular vesicles to recessive dystrophic epidermolysis bullosa fibroblasts. Biochimie. 2018;155:50–58. doi:10.1016/j.biochi.2018.04.007
   PubMed Web of Science ®Google Scholar
• Conget P, Rodriguez F, Kramer S, et al. Replenishment of type VII collagen and re-epithelialization of chronically ulcerated skin after intradermal administration of allogeneic mesenchymal stromal cells in two patients with recessive dystrophic epidermolysis bullosa. Cytotherapy. 2010;12(3):429–431. doi:10.3109/14653241003587637
   PubMed Web of Science ®Google Scholar
• El-Darouti M, Fawzy M, Amin I, et al. Treatment of dystrophic epidermolysis bullosa with bone marrow non-hematopoeitic stem cells: a randomized controlled trial. Dermatol Ther. 2016;29(2):96–100. doi:10.1111/dth.12305
   PubMed Web of Science ®Google Scholar
• Petrof G, Lwin SM, Martinez-Queipo M, et al. Potential of systemic allogeneic mesenchymal stromal cell therapy for children with recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2015;135(9):2319–2321. doi:10.1038/jid.2015.158
   PubMed Web of Science ®Google Scholar
• Rashidghamat E, Kadiyirire T, Ayis S, et al. Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 2020;83(2):447–454. doi:10.1016/j.jaad.2019.11.038
   PubMed Web of Science ®Google Scholar
• Lee SE, Lee SJ, Kim SE, et al. Intravenous allogeneic umbilical cord blood-derived mesenchymal stem cell therapy in recessive dystrophic epidermolysis bullosa patients. JCI Insight. 2021;6(2):e143606. doi:10.1172/jci.insight.143606
   PubMed Web of Science ®Google Scholar
• Fujita Y, Nohara T, Takashima S, et al. Intravenous allogeneic multilineage-differentiating stress-enduring cells in adults with dystrophic epidermolysis bullosa: a phase 1/2 open-label study. J Eur Acad Dermatol Venereol. 2021;35(8):e528–e531. doi:10.1111/jdv.17201
   PubMed Web of Science ®Google Scholar
• Webber BR, O’Connor KT, McElmurry RT, et al. Rapid generation of Col7a1(-/-) mouse model of recessive dystrophic epidermolysis bullosa and partial rescue via immunosuppressive dermal mesenchymal stem cells. Lab Invest. 2017;97(10):1218–1224. doi:10.1038/labinvest.2017.85
   PubMed Web of Science ®Google Scholar
• Riedl J, Pickett-Leonard M, Eide C, et al. ABCB5+ dermal mesenchymal stromal cells with favorable skin homing and local immunomodulation for recessive dystrophic epidermolysis bullosa treatment. Stem Cells. 2021;39(7):897–903. doi:10.1002/stem.3356
   PubMed Web of Science ®Google Scholar
• Lai RC, Yeo RW, Lim SK. Mesenchymal stem cell exosomes. Semin Cell Dev Biol. 2015;40:82–88. doi:10.1016/j.semcdb.2015.03.001
   PubMed Web of Science ®Google Scholar
• Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750 doi:10.1080/20013078.2018.1535750.
   PubMed Web of Science ®Google Scholar
• O’Brien K, Breyne K, Ughetto S, Laurent LC, Breakefield XO. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 2020;21(10):585–606 doi:10.1038/s41580-020-0251-y.
   PubMed Web of Science ®Google Scholar
• Bray ER, Kirsner RS, Badiavas EV. Mesenchymal stem cell-derived extracellular vesicles as an advanced therapy for chronic wounds. Cold Spring Harb Perspect Biol. 2022;14(10):a041227 doi:10.1101/cshperspect.a041227.
   PubMed Web of Science ®Google Scholar
• Gebara N, Rossi A, Skovronova R, Aziz JM, Asthana A, Bussolati B. Extracellular vesicles, apoptotic bodies and mitochondria: stem cell bioproducts for organ regeneration. Curr Transplant Rep. 2020;7:105–113 doi:10.1007/s40472-020-00282-2.
   Google Scholar
• Woodley DT, Keene DR, Atha T, et al. Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa. Nat Med. 2004;10(7):693–695 doi:10.1038/nm1063.
   PubMed Web of Science ®Google Scholar
• Hou Y, Guey LT, Wu T, et al. Intravenously administered recombinant human type VII collagen derived from Chinese hamster ovary cells reverses the disease phenotype in recessive dystrophic epidermolysis bullosa mice. J Invest Dermatol. 2015;135(12):3060–3067. doi:10.1038/jid.2015.291
   PubMed Web of Science ®Google Scholar
• Woodley DT, Wang X, Amir M, et al. Intravenously injected recombinant human type VII collagen homes to skin wounds and restores skin integrity of dystrophic epidermolysis bullosa. J Invest Dermatol. 2013;133(7):1910–1913 doi:10.1038/jid.2013.10.
   PubMed Web of Science ®Google Scholar
• Bruckner A, Tang J, Chung W, et al. Collagen 7 (C7) protein replacement therapy (PTR-01) durably reduces wound size and symptoms in patients with recessive dystrophic epidermolysis bullosa (RDEB). J Invest Dermatol. 2022;142(8):S50. doi:10.1016/j.jid.2022.05.303
   Web of Science ®Google Scholar
• Andersson U, Yang H, Harris H. High-mobility group box 1 protein (HMGB1) operates as an alarmin outside as well as inside cells. Semin Immunol. 2018;38:40–48. doi:10.1016/j.smim.2018.02.011
   PubMed Web of Science ®Google Scholar
• Tamai K, Yamazaki T, Chino T, et al. PDGFRalpha-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia. Proc Natl Acad Sci U S A. 2011;108(16):6609–6614. doi:10.1073/pnas.1016753108
   PubMed Web of Science ®Google Scholar
• Goto T, Miyagawa S, Tamai K, et al. High-mobility group box 1 fragment suppresses adverse post-infarction remodeling by recruiting PDGFRα-positive bone marrow cells. PLoS One. 2020;15(4):e0230392. doi:10.1371/journal.pone.0230392
   PubMed Web of Science ®Google Scholar
• Kido T, Miyagawa S, Goto T, et al. The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster. PLoS One. 2018;13(12):e0202838. doi:10.1371/journal.pone.0202838
   PubMed Web of Science ®Google Scholar
• Odorisio T, Di Salvio M, Orecchia A, et al. Monozygotic twins discordant for recessive dystrophic epidermolysis bullosa phenotype highlight the role of TGF-β signalling in modifying disease severity. Hum Mol Genet. 2014;23(15):3907–3922. doi:10.1093/hmg/ddu102
   PubMed Web of Science ®Google Scholar
• Lim DS, Lutucuta S, Bachireddy P, et al. Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation. 2001;103(6):789–791. doi:10.1161/01.CIR.103.6.789
   PubMed Web of Science ®Google Scholar
• Nyström A, Thriene K, Mittapalli V, et al. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms. EMBO Mol Med. 2015;7(9):1211–1228. doi:10.15252/emmm.201505061
   PubMed Web of Science ®Google Scholar
• Pourani MR, Vahidnezhad H, Mansouri P, et al. Losartan treatment improves recessive dystrophic epidermolysis bullosa: a case series. Dermatol Ther. 2022;35(7):e15515. doi:10.1111/dth.15515
   PubMed Web of Science ®Google Scholar
• Kiritsi D. Losartan for RDEB trial – results and international perspectives. EB2020 1st World Congress on Epidermolysis Bullosa; 2020 Jan 19–23; London, UK. Acta Derm Venereol. 2020;100:1–7 doi:10.2340/00015555-3586
   Web of Science ®Google Scholar
• Oldakovskiy V, Murashkin N, Lokhmatov M, et al. Our experience of using losartan for esophageal stenosis in children with dystrophic form of congenital epidermolysis bullosa. J Pediatr Surg. 2023;58(4):619–623. doi:10.1016/j.jpedsurg.2022.11.001
   PubMed Web of Science ®Google Scholar
• Relvas M, Figueiredo AC, Calado R, Calvão J, Ramos L. Losartan as therapy for recessive dystrophic epidermolysis bullosa: report of three cases. Dermatol Ther. 2022;35(9):e15678. doi:10.1111/dth.15678
   PubMed Web of Science ®Google Scholar
• Cianfarani F, De Domenico E, Nyström A, et al. Decorin counteracts disease progression in mice with recessive dystrophic epidermolysis bullosa. Matrix Biol. 2019;81:3–16. doi:10.1016/j.matbio.2018.12.001
   PubMed Web of Science ®Google Scholar
• Pemmari T, Ivanova L, May U, et al. Exposed CendR domain in homing peptide yields skin-targeted therapeutic in epidermolysis bullosa. Mol Ther. 2020;28(8):1833–1845. doi:10.1016/j.ymthe.2020.05.017
   PubMed Web of Science ®Google Scholar
• Papanikolaou M, Onoufriadis A, Mellerio JE, et al. Prevalence, pathophysiology and management of itch in epidermolysis bullosa. Br J Dermatol. 2021;184(5):816–825. doi:10.1111/bjd.19496
   PubMed Web of Science ®Google Scholar
• Kaushik A, Mahajan R, Karim A, Handa S, De D, Saikia B. Successful use of cyclosporine in epidermolysis bullosa pruriginosa. Dermatol Ther. 2020;33(6):e14489. doi:10.1111/dth.14489
   PubMed Web of Science ®Google Scholar
• Pallesen KAU, Lindahl KH, Bygum A. Dominant dystrophic epidermolysis bullosa pruriginosa responding to naltrexone treatment. Acta Derm Venereol. 2019;99(12):1195–1196. doi:10.2340/00015555-3304
   PubMed Web of Science ®Google Scholar
• Quintana BR, Durán EP, Pérez Cejudo JA. Successful control of recalcitrant pruritus in epidermolysis bullosa pruriginosa with dupilumab. Actas Dermosifiliogr. 2023. doi:10.1016/j.ad.2022.05.045
   Web of Science ®Google Scholar
• Wu PC, Dai YX, Li CL, Chen CC, Chang YT, Ma SH. Dupilumab zur behandlung von genodermatosen: eine systematische ìbersicht. J Dtsch Dermatol Ges. 2023;21(1):7–18 doi:10.1111/ddg.14924_g.
   Web of Science ®Google Scholar
• Yu L, Wang J, Bian L, et al. Dystrophic epidermolysis bullosa pruriginosa: successfully treated with dupilumab. Dermatitis. 2023;34(1):58–59. doi:10.1089/DERM.0000000000000954
   PubMed Web of Science ®Google Scholar
• Caroppo F, Milan E, Giulioni E, Belloni Fortina A. A case of dystrophic epidermolysis bullosa pruriginosa treated with dupilumab. J Eur Acad Dermatol Venereol. 2022;36(5):e365–e367. doi:10.1111/jdv.17887
   PubMed Web of Science ®Google Scholar
• Darbord D, Hickman G, Pironon N, et al. Dystrophic epidermolysis bullosa pruriginosa: a new case series of a rare phenotype unveils skewed Th2 immunity. J Eur Acad Dermatol Venereol. 2022;36(1):133–143. doi:10.1111/jdv.17671
   PubMed Web of Science ®Google Scholar
• Wang Y, Zhou M, Zhang L, Zheng S, Hong Y, Gao XH. Amelioration of dystrophic epidermolysis bullosa pruriginosa symptoms with dupilumab: a case report. Dermatol Ther. 2021;34(6):e15130. doi:10.1111/dth.15130
   PubMed Web of Science ®Google Scholar
• Clawson RC, Duran SF, Pariser RJ. Epidermolysis bullosa pruriginosa responding to dupilumab. JAAD Case Rep. 2021;16:69–71. doi:10.1016/j.jdcr.2021.07.036
   PubMedGoogle Scholar
• Zhou AG, Little AJ, Antaya RJ. Epidermolysis bullosa pruriginosa treated with dupilumab. Pediatr Dermatol. 2021;38(2):526–527. doi:10.1111/pde.14493
   PubMed Web of Science ®Google Scholar
• Shehadeh W, Sarig O, Bar J, Sprecher E, Samuelov L. Treatment of epidermolysis bullosa pruriginosa-associated pruritus with dupilumab. Br J Dermatol. 2020;182(6):1495–1497. doi:10.1111/bjd.18855
   PubMed Web of Science ®Google Scholar
• Chen F, Guo Y, Zhou K, et al. The clinical efficacy and safety of anti-IgE therapy in recessive dystrophic epidermolysis bullosa. Clin Genet. 2022;101(1):110–115. doi:10.1111/cge.14062
   PubMed Web of Science ®Google Scholar
• Jiang X, Wang H, Lee M, Lin Z. Epidermolysis bullosa pruriginosa treated with baricitinib. JAMA Dermatol. 2021;157(10):1243–1244. doi:10.1001/jamadermatol.2021.3174
   PubMed Web of Science ®Google Scholar
• Chen KJ, Fang S, Ye Q, Jia M. Successful use of tofacitinib in epidermolysis bullosa pruriginosa. Clin Exp Dermatol. 2022;47(3):598–600. doi:10.1111/ced.14998
   PubMed Web of Science ®Google Scholar
• Chelliah MP, Zinn Z, Khuu P, Teng JMC. Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. Pediatr Dermatol. 2018;35(4):e224–e227. doi:10.1111/pde.13545
   PubMed Web of Science ®Google Scholar
• Schräder NHB, Duipmans JC, Molenbuur B, Wolff AP, Jonkman MF. Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases. Br J Dermatol. 2019;180(4):922–924. doi:10.1111/bjd.17341
   PubMed Web of Science ®Google Scholar
• Schräder NHB, Gorell ES, Stewart RE, et al. Cannabinoid use and effects in patients with epidermolysis bullosa: an international cross-sectional survey study. Orphanet J Rare Dis. 2021;16(1):377. doi:10.1186/s13023-021-02010-0
   PubMed Web of Science ®Google Scholar
• Schräder NHB, Duipmans JC, Renken RJ, et al. The C4EB study-transvamix (10% THC / 5% CBD) to treat chronic pain in epidermolysis bullosa: a protocol for an explorative randomized, placebo controlled, and double blind intervention crossover study. PLoS One. 2022;17(12):e0277512. doi:10.1371/journal.pone.0277512
   PubMedGoogle Scholar
• Onoufriadis A, Proudfoot LE, Ainali C, et al. Transcriptomic profiling of recessive dystrophic epidermolysis bullosa wounded skin highlights drug repurposing opportunities to improve wound healing. Exp Dermatol. 2022;31(3):420–426. doi:10.1111/exd.14481
   PubMed Web of Science ®Google Scholar
• Haghighi Javid A, Li D, Technau-Hafsi K, Has C. IL-17A immune pattern across genetic acantholytic and blistering disorders. Clin Exp Dermatol. 2023;48(5):llad012 doi:10.1093/ced/llad012.
   Web of Science ®Google Scholar
• Castela E, Tulic MK, Rozières A, et al. EBS generalized severe is an inflammatory disease. Br J Dermatol. 2019;180:357–364. doi:10.1111/bjd.16897
   PubMed Web of Science ®Google Scholar
• Scheffler A. The wound healing properties of betulin from birch bark from bench to bedside. Planta Med. 2019;85(7):524–527. doi:10.1055/a-0850-0224
   PubMed Web of Science ®Google Scholar
• Schwieger-Briel A, Ott H, Kiritsi D, Laszczyk-Lauer M, Bodemer C. Mechanism of Oleogel-S10: a triterpene preparation for the treatment of epidermolysis bullosa. Dermatol Ther. 2019;32(4):e12983. doi:10.1111/dth.12983
   PubMed Web of Science ®Google Scholar
• Schwieger-Briel A, Kiritsi D, Schempp C, Has C, Schumann H. Betulin-based Oleogel to improve wound healing in dystrophic epidermolysis bullosa: a prospective controlled proof-of-concept study. Dermatol Res Pract. 2017;2017:5068969. doi:10.1155/2017/5068969
   PubMed Web of Science ®Google Scholar
• Kern JS, Sprecher E, Fernandez MF, et al. Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study. Br J Dermatol. 2023;188(1):12–21. doi:10.1093/bjd/ljac001
   PubMed Web of Science ®Google Scholar
• Takahashi H, Ibe M, Kinouchi M, Ishida-Yamamoto A, Hashimoto Y, Iizuka H. Similarly potent action of 1,25-dihydroxyvitamin D3 and its analogues, tacalcitol, calcipotriol, and maxacalcitol on normal human keratinocyte proliferation and differentiation. J Dermatol Sci. 2003;31(1):21–28. doi:10.1016/S0923-1811(02)00136-6
   PubMed Web of Science ®Google Scholar
• Guttmann-Gruber C, Tockner B, Scharler C, et al. Low-dose calcipotriol can elicit wound closure, anti-microbial, and anti-neoplastic effects in epidermolysis bullosa keratinocytes. Sci Rep. 2018;8(1):13430. doi:10.1038/s41598-018-31823-6
   PubMedGoogle Scholar
• Guttmann-Gruber C, Piñón Hofbauer J, Tockner B, et al. Impact of low-dose calcipotriol ointment on wound healing, pruritus and pain in patients with dystrophic epidermolysis bullosa: a randomized, double-blind, placebo-controlled trial. Orphanet J Rare Dis. 2021;16(1):473. doi:10.1186/s13023-021-02062-2
   PubMed Web of Science ®Google Scholar
• Minicucci EM, Barraviera SR, Miot H, Almeida-Lopes L. Low-level laser therapy for the treatment of epidermolysis bullosa: a case report. J Cosmet Laser Ther. 2010;12(4):203–205. doi:10.3109/14764172.2010.502460
   PubMed Web of Science ®Google Scholar
• Krakowski AC, Ghasri P. Case report: rapidly healing epidermolysis bullosa wound after ablative fractional resurfacing. Pediatrics. 2015;135(1):e207–e210. doi:10.1542/peds.2014-1779
   PubMed Web of Science ®Google Scholar
• Garza-Mayers AC, Su KA, Wiss K. Improved erythema and decreased blister formation in dominant dystrophic epidermolysis bullosa following treatment with pulsed dye laser. Pediatr Dermatol. 2022;39(6):1005–1006. doi:10.1111/pde.15126
   PubMed Web of Science ®Google Scholar