Progress toward Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015

Jouni Uitto, Leena Bruckner-Tuderman, Angela M Christiano, John A McGrath, Cristina Has, Andrew P South, Brett Kopelan, E Clare Robinson, Jouni Uitto, Leena Bruckner-Tuderman, Angela M Christiano, John A McGrath, Cristina Has, Andrew P South, Brett Kopelan, E Clare Robinson

Abstract

Epidermolysis bullosa (EB), a group of complex heritable blistering diseases, is the topic of triennial research meetings organized by DEBRA International, Vienna, Austria, the network of national EB patient advocacy organizations. The DEBRA 2015 Research Conference, held in May 2015, brought together investigators and clinicians from around the world working at the forefront of EB research. Discussing the state-of-the-art approaches from a wide range of disciplines, there was a palpable excitement at this conference brought about by the optimism about applying new sequencing techniques, genome editing, protein replacement, autologous and allogeneic stem cell therapy, innovations in cancer biology, revertant mosaicism, and induced pluripotent stem cell techniques, all of which are aimed at developing new therapies for EB. Many in the field who have participated in EB research for many years were especially enthusiastic and felt that, possibly for the first time, the field seems uniquely poised to bring these new tools to effectively tackle EB. Multiple complementary approaches are currently in motion toward improved quality of life and eventually a cure for patients suffering from EB, a currently intractable disease.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Participants in the EB2015 Research Symposium held in Braselton, GA, in May 2015.

References

    1. Albrengues J, Bourget I, Pons C, et al. LIF mediates proinvasive activation of stromal fibroblasts in cancer. Cell Rep. 2014;7:1664–78.
    1. Arbiser JL, Fan CY, Su X, et al. Involvement of p53 and p16 tumor suppressor genes in recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma. J Invest Dermatol. 2004;123:788–90.
    1. Bidou L, Allamand V, Rousset JP, et al. Sense from nonsense: therapies for premature stop codon diseases. Trends Mol Med. 2012;18:679–88.
    1. Bohnekamp J, Cryderman DE, Paululat A, et al. A drosophila model of epidermolysis bullosa simplex. J Invest Dermatol. 2015;135:2031–9.
    1. Bruckner-Tuderman L, McGrath JA, Robinson EC, et al. Animal models of epidermolysis bullosa: update 2010. J Invest Dermatol. 2010;130:1485–8.
    1. Bruckner-Tuderman L, McGrath JA, Robinson EC, et al. Progress in epidermolysis bullosa research: Summary of DEBRA International Research Conference 2012. J Invest Dermatol. 2013;133:2121–6.
    1. 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;12:429–31.
    1. Duarte B, Miselli F, Murillas R, et al. Long-term skin regeneration from a gene-targeted human epidermal stem cell clone. Mol Ther. 2014;22:1878–80.
    1. 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. 2015 in press.
    1. Fine JD, Johnson LB, Weiner M, et al. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol. 2009;60:203–11.
    1. Fritsch A, Loeckermann S, Kern JS, et al. A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy. J Clin Invest. 2008;118:1669–79.
    1. 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;167:765–9.
    1. Gostynski A, Deviaene FC, Pasmooij AM, et al. Adhesive stripping to remove epidermis in junctional epidermolysis bullosa for revertant cell therapy. Br J Dermatol. 2009;161:444–7.
    1. Gostynski A, Pasmooij AM, Jonkman MF. Successful therapeutic transplantation of revertant skin in epidermolysis bullosa. J Am Acad Dermatol. 2014;70:98–101.
    1. Heinonen S, Männikkö M, Klement JF, et al. Targeted inactivation of the type VII collagen gene (Col7a1) in mice results in severe blistering phenotype: a model for recessive dystrophic epidermolysis bullosa. J Cell Sci. 1999;112:3641–8.
    1. Hoste E, Arwert EN, Lal R, et al. Innate sensing of microbial products promotes wound-induced skin cancer. Nat Commun. 2015;6:5932.
    1. 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 in press.
    1. Hurskainen T, Kokkonen N, Sormunen R, et al. Deletion of the major bullous pemphigoid epitope region of collagen XVII induces blistering, autoimmunization, and itching in mice. J Invest Dermatol. 2015;135:1303–10.
    1. Hüttner C, Gruber C, Lang R, et al. Expression and regulation of cathelicidin in keratinocytes from patients with epidermolysis bullosa. J Invest Dermatol. 2012;132:S7–S13.
    1. Iinuma S, Aikawa E, Tamai K, et al. Transplanted bone marrow-derived circulating PDGFRalpha+ cells restore type VII collagen in recessive dystrophic epidermolysis bullosa mouse skin graft. J Immunol. 2015;194:1996–2003.
    1. Jonkman MF, Scheffer H, Stulp R, et al. Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion. Cell. 1997;88:543–51.
    1. Kim SH, Choi HY, So JH, et al. Zebrafish type XVII collagen: gene structures, expression profiles, and morpholino “knock-down” phenotypes. Matrix Biol. 2010;29:629–37.
    1. Kiritsi D, Garcia M, Brander R, et al. Mechanisms of natural gene therapy in dystrophic epidermolysis bullosa. J Invest Dermatol. 2014;134:2097–104.
    1. Koller U, Hainzl S, Kocher T, et al. Trans-splicing improvement by the combined application of antisense strategies. Int J Mol Sci. 2015;16:1179–91.
    1. Küttner V, Mack C, Rigbolt KTG, et al. Global remodeling of cellular microenvironment due to loss of collagen VII. Mol Syst Biol. 2013 Online Publication 16.04.2013, DOI:MSB2013.17.
    1. Li Q, Uitto J. Zebrafish as a model system to study skin biology and pathology. J Invest Dermatol. 2014;134:e21.
    1. Liao Y, Itoh M, Yang A, et al. Human cord blood-derived unrestricted somatic stem cells promote wound healing and have therapeutic potential for patients with recessive dystrophic epidermolysis bullosa. Cell Transplant. 2014;23:303–17.
    1. Liao Y, Ivanova L, Zhu H, et al. Rescue of the mucocutaneous manifestations by human cord blood derived nonhematopoietic stem cells in a mouse model of recessive dystrophic epidermolysis bullosa. Stem Cells. 2015;33:1807–17.
    1. Martincorena I, Roshan A, Gerstung M, et al. Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science. 2015;348:880–6.
    1. Mellerio JE, Robertson SJ, Bernardis C, et al. Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa - best clinical practice guidelines. Br J Dermatol. 2015 in press.
    1. Moniaga CS, Egawa G, Miyachi Y, et al. Calcipotriol modulates IL-22 receptor expression and keratinocyte proliferation in IL-22-induced epidermal hyperplasia. J Dermatol Sci. 2013;71:76–7.
    1. 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;131:1771–4.
    1. Ng YZ, Pourreyron C, Salas-Alanis JC, et al. Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa. Cancer Res. 2012;72:3522–34.
    1. Nyström A, Thriene K, Mittapalli V, et al. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms. EMBO Mol Med. 2015;7:1211–28.
    1. Nyström A, Velati D, Mittapalli VR, et al. Collagen VII plays a dual role in wound healing. J Clin Invest. 2013;123:3498–509.
    1. Pasmooij AM, Jonkman MF, Uitto J. Revertant mosaicism in heritable skin diseases: mechanisms of natural gene therapy. Discov Med. 2012;14:167–79.
    1. Perdoni C, McGrath JA, Tolar J. Preconditioning of mesenchymal stem cells for improved transplantation efficacy in recessive dystrophic epidermolysis bullosa. Stem Cell Res Ther. 2014;5:121.
    1. 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;135:2319–21.
    1. Petrof G, Martinez-Queipo M, Mellerio JE, et al. Fibroblast cell therapy enhances initial healing in recessive dystrophic epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial. Br J Dermatol. 2013;169:1025–33.
    1. Pourreyron C, Cox G, Mao X, et al. Patients with recessive dystrophic epidermolysis bullosa develop squamous-cell carcinoma regardless of type VII collagen expression. J Invest Dermatol. 2007;127:2438–44.
    1. Remington J, Wang X, Hou Y, et al. Injection of recombinant human type VII collagen corrects the disease phenotype in a murine model of dystrophic epidermolysis bullosa. Mol Ther. 2009;17:26–33.
    1. Sebastiano V, Zhen HH, Haddad B, et al. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa. Sci Transl Med. 2014;6:264ra163.
    1. Sproule TJ, Bubier JA, Grandi FC, et al. Molecular identification of collagen17a1 as a major genetic modifier of laminin gamma 2 mutation-induced junctional epidermolysis bullosa in mice. PLoS Genet. 2014;10:e1004068.
    1. Tamai K, Yamazaki T, Chino T, et al. PDGFR{alpha}-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;108:6609–14.
    1. Tolar J, McGrath J, Keene DR. Hematopoietic and mesenchymal cell transplantation after myeloablative and non-myeloablative conditioning for recessive dystrophic and junctional epidermolysis bullosa (RDEB, JEB). J Invest Dermatol. 2012;132:A534. (Abstract)
    1. Tolar J, McGrath JA, Xia L, et al. Patient-specific naturally gene-reverted induced pluripotent stem cells in recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2014;134:1246–54.
    1. Turczynski S, Titeux M, Pironon N, et al. Antisense-mediated exon skipping to reframe transcripts. Methods Mol Biol. 2012;867:221–38.
    1. Uitto J, McGrath JA, Rodeck U, et al. Progress in epidermolysis bullosa research: toward treatment and cure. J Invest Dermatol. 2010;130:1778–84.
    1. Umegaki-Arao N, Pasmooij AM, Itoh M, et al. Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa. Sci Transl Med. 2014;6:264ra164.
    1. 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;69:898–908 e7.
    1. Wagner JE, Ishida-Yamamoto A, McGrath JA, et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N Engl J Med. 2010;363:629–39.
    1. Wally V, Kitzmueller S, Lagler F, et al. Topical diacerein for epidermolysis bullosa: a randomized controlled pilot study. Orphanet J Rare Dis. 2013;8:69.
    1. Wang NJ, Sanborn Z, Arnett KL, et al. Loss-of-function mutations in Notch receptors in cutaneous and lung squamous cell carcinoma. Proc Natl Acad Sci USA. 2011;108:17761–6.
    1. Wang X, Ghasri P, Amir M, et al. Topical application of recombinant type VII collagen incorporates into the dermal-epidermal junction and promotes wound closure. Mol Ther. 2013;21:1335–44.
    1. Wenzel D, Bayerl J, Nystrom A, et al. Genetically corrected iPSCs as cell therapy for recessive dystrophic epidermolysis bullosa. Sci Transl Med. 2014;6:264ra165.
    1. Winter L, Staszewska I, Mihailovska E, et al. Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle. J Clin Invest. 2014;124:1144–57.
    1. Wong T, Gammon L, Liu L, et al. Potential of fibroblast cell therapy for recessive dystrophic epidermolysis bullosa. J Invest Dermatol. 2008;128:2179–89.
    1. 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;133:1910–3.

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