Editorial Material
Medicine, Research & Experimental
Christen L. Ebens
Summary: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic blistering skin disease caused by biallelic mutations in the COL7A1 gene. Clinical manifestations include fragile skin, pain, itch, high metabolic demand, and dermal fibrosis.
EMBO MOLECULAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Franciscus C. Vermeer, Jeroen Bremer, Robert J. Sietsma, Aileen Sandilands, Robyn P. Hickerson, Marieke C. Bolling, Anna M. G. Pasmooij, Henny H. Lemmink, Morris A. Swertz, Nine V. A. M. Knoers, K. Joeri van der Velde, Peter C. van den Akker
Summary: Epidermolysis bullosa is a genetic skin condition characterized by skin fragility caused by gene variants, with treatment currently focused on symptom relief. Exon skipping shows potential as a therapeutic strategy for EB, with the severity of the disease linked to gene involvement and variants.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Dermatology
K. S. Subramaniam, M. N. Antoniou, J. A. McGrath, S. M. Lwin
Summary: Epidermolysis bullosa (EB) is a group of inherited skin disorders with debilitating consequences. Recessive dystrophic EB (RDEB) is especially severe and can lead to chronic wounds and squamous cell carcinoma. Advances in molecular genetics and biotechnology have paved the way for gene and cell-based therapies for EB, and RDEB has become the focus of clinical trials. There is a global effort involving academia, industry, and patient organizations to develop targeted therapeutics for EB. Dermatologists should familiarize themselves with gene therapy and its applications.
BRITISH JOURNAL OF DERMATOLOGY
(2022)
Article
Dermatology
Christine Gretzmeier, Didier Pin, Johannes S. Kern, Mei Chen, David T. Woodley, Leena Bruckner-Tuderman, Mark P. de Souza, Alexander Nystroem
Summary: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin disease characterized by skin blistering and fibrosis. This study found that intravenous administration of recombinant C7 can reduce fibrosis in RDEB patients, and this treatment method is well-tolerated in mice and dogs.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Dermatology
S. J. Robertson, C. Prodinger, L. Liu, C. Skilbeck, G. Petrof, A. E. Martinez, J. E. Mellerio, D. T. Greenblatt
Summary: The rare inversa subtype of recessive dystrophic epidermolysis bullosa (RDEB-I) is characterized by predominant intertriginous skin blistering and marked mucosal involvement. This study found a higher prevalence of otological complications in RDEB-I patients than previously reported, and presented the first case of cholesteatoma in RDEB-I. Bone-anchored hearing aids (BAHA) and middle ear implants (MEI) were identified as safe and effective treatment options for hearing loss in RDEB-I patients.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Jose Bonafont, Angeles Mencia, Esteban Chacon-Solano, Wai Srifa, Sriram Vaidyanathan, Rosa Romano, Marta Garcia, Rosario Hervas-Salcedo, Laura Ugalde, Blanca Duarte, Matthew H. Porteus, Marcela Del Rio, Fernando Larcher, Rodolfo Murillas
Summary: This study presents a gene-editing approach using CRISPR-Cas9 system to achieve gene correction in different cell types, showing therapeutic potential for RDEB.
Review
Biochemistry & Molecular Biology
Grace Tartaglia, Qingqing Cao, Zachary M. Padron, Andrew P. South
Summary: RDEB is a devastating skin blistering disease caused by mutations in the C7 gene, leading to rapid fibrosis development, chronic wounds, and squamous cell carcinoma. It serves as a model for understanding the molecular basis of fibrosis and rapidly developing aggressive cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Dermatology
Mohammad Reza Pourani, Hassan Vahidnezhad, Parvin Mansouri, Leila Youssefian, Azadeh Rakhshan, Behzad Hajimoradi, Fahimeh Abdollahimajd, Jouni Uitto
Summary: This case series reports the beneficial effects of losartan on RDEB as a potentially novel treatment. Losartan can improve the clinical features and severity of the disease, and enhance the quality of life for patients with RDEB.
DERMATOLOGIC THERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Sung-Ah Hong, Song-Ee Kim, A-Young Lee, Gue-Ho Hwang, Jong Hoon Kim, Hiroaki Iwata, Soo-Chan Kim, Sangsu Bae, Sang Eun Lee
Summary: In this study, researchers identified and corrected pathogenic mutations in the COL7A1 gene using adenine base editors and prime editors in patients with recessive dystrophic epidermolysis bullosa (RDEB). The edited patient-derived skin equivalents showed positive outcomes in terms of C7 deposition and anchoring fibril formation, suggesting the feasibility of ex vivo gene editing as a potential treatment for RDEB.
Article
Biochemistry & Molecular Biology
Avina Rami, Lukasz Laczmanski, Jagoda Jackow-Nowicka, Joanna Jackow
Summary: A model for studying the development of RDEB-cSCC was established using cellular reprogramming and re-differentiation technology. RNA-seq analysis revealed distinct gene expression signatures and functional changes in RDEB-cSCC subjected to reprogramming and re-differentiation, offering a valuable tool to study cSCC and identify potential therapeutic targets for RDEB-cSCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Dermatology
Leonie Huitema, Taylor Phillips, Vitali Alexeev, Olga Igoucheva
Summary: Hereditary epidermolysis bullosa is a mechanobullous skin fragility disorder characterized by skin blistering under mechanical stress, with no cure currently available. Recent data suggest systemic immunological defects in patients, particularly affecting antibacterial immunity.
EXPERIMENTAL DERMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Irina Gurevich, Pooja Agarwal, PeiPei Zhang, John A. Dolorito, Stacie Oliver, Henry Liu, Nicholas Reitze, Nikhil Sarma, Isin Sinem Bagci, Kunju Sridhar, Visesha Kakarla, Vamsi K. Yenamandra, Mark O'Malley, Marco Prisco, Sara F. Tufa, Douglas R. Keene, Andrew P. South, Suma M. Krishnan, M. Peter Marinkovich
Summary: This study evaluated the use of an engineered viral vector, B-VEC, for the treatment of recessive dystrophic epidermolysis bullosa (RDEB) patients with wounds. The results showed that B-VEC promotes wound healing and is well-tolerated.
Article
Dermatology
Yasushi Kikuchi, Tomoki Tamakoshi, Ryuichi Ishida, Ryosuke Kobayashi, Shiho Mori, Akemi Ishida-Yamamoto, Manabu Fujimoto, Yasufumi Kaneda, Katsuto Tamai
Summary: In this study, researchers developed an ex vivo gene therapy for recessive dystrophic epidermolysis bullosa (RDEB) using autologous mesenchymal stromal cells (MSCs). The gene-modified MSCs were injected into mice with type VII collagen deficiency, leading to continuous and widespread expression of type VII collagen. The therapy showed successful application in both early blistering skin and advanced ulcerative lesions in the RDEB mouse model.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Medicine, Research & Experimental
Sang Eun Lee, Seung-Ju Lee, Song-Ee Kim, Kinam Kim, Boyoung Cho, Kyounghwan Roh, Soo-Chan Kim
Summary: This study evaluated the safety and potential clinical efficacy of intravenous infusion of allogeneic human umbilical cord blood-derived mesenchymal stem cells in patients with Recessive Dystrophic Epidermolysis Bullosa (RDEB). The results showed that the treatment was well tolerated and led to transient clinical benefits, including improvements in wound conditions, pain, itch, and quality of life. Inflammatory skin conditions and C7 expression also showed some improvement after treatment.
Article
Dermatology
Kirk Twaroski, Weili Chen, Michael Pickett-Leonard, Jakub Tolar
Summary: Squamous cell carcinoma (SCC) occurs in over 80% of individuals with recessive dystrophic epidermolysis bullosa (RDEB), leading to high metastatic tendencies and low survival rates. Research has shown that TGF beta 1 secreted by RDEB fibroblasts plays a crucial role in inducing migration and invasion in RDEB-SCC, and these effects can be reversed by inhibiting TGF beta signaling and downstream pathways.
EXPERIMENTAL DERMATOLOGY
(2021)
Editorial Material
Cell Biology
Eric Delpire, Thomas J. Hawke, Mythreye Karthikeyan, Wei Kong, Alexander Nystroem, Shizuka Uchida, Liliana Schaefer
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Review
Dermatology
Eva W. H. Korte, Tobias Welponer, Jan Kottner, Sjoukje van der Werf, Peter C. van den Akker, Barbara Horvath, Dimitra Kiritsi, Martin Laimer, Anna M. G. Pasmooij, Verena Wally, Maria C. Bolling
Summary: This study summarizes the different outcomes and outcome measurement instruments reported in clinical research on epidermolysis bullosa (EB) over the past 30 years and identifies a significant heterogeneity. Adequate evaluation and comparison of EB clinical studies require well-defined and consensus-endorsed outcomes and measurement instruments. This scoping review is the first step towards harmonization of EB outcomes, which is crucial for the clinical translation of novel treatments.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Janine Zwicklhuber, Thomas Kocher, Bernadette Liemberger, Stefan Hainzl, Johannes Bischof, Dirk Strunk, Anna M. Raninger, Iris Gratz, Verena Wally, Christina Guttmann-Gruber, Josefina Pinon Hofbauer, Johann W. Bauer, Ulrich Koller
Summary: In this study, a cell line suitable for gene expression studies of the JEB-associated COL17A1 gene was developed using the CRISPR/Cas9 system. The accurate expression and localization of the GFP-C17 fusion protein were confirmed. Repairing a JEB-associated frameshift mutation restored the expression and localization of the fusion protein. This fluorescence-based JEB cell line has the potential to be used for personalized gene editing and applications in vitro and in animal models in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Temitope Esho, Birgit Kobbe, Sara F. Tufa, Douglas R. Keene, Mats Paulsson, Raimund Wagener
Summary: AMACO is strongly expressed at basement membranes during embryonic development and associates with proteins of the Fraser complex in skin. However, AMACO-deficient mice lack an obvious phenotype and the formation and function of anchoring cords are not affected. This suggests that AMACO is not essential for the process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Dermatology
Andrew P. South, Martin Laimer, Mouhamed Gueye, Jennifer Y. Sui, Lawrence F. Eichenfield, Jemima E. Mellerio, Alexander Nystrom
Summary: Dystrophic epidermolysis bullosa is a rare genetic skin disorder caused by COL7A1 sequence variations. One serious complication of this disorder is cutaneous squamous cell carcinoma. Type VII collagen deficits alter signaling and promote the progression of cutaneous squamous cell carcinoma. This review examines the pathophysiology of cutaneous squamous cell carcinoma in dystrophic epidermolysis bullosa and explores ways to reduce the risk of this cancer.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Oncology
Dino Bekric, Daniel Neureiter, Celina Ablinger, Heidemarie Dobias, Marlena Beyreis, Markus Ritter, Martin Jakab, Johannes Bischof, Ulrich Koller, Tobias Kiesslich, Christian Mayr
Summary: Treating biliary tract cancer (BTC) is challenging due to late diagnosis and resistance to current therapies. In this study, we investigate the potential of tazemetostat, an EZH2-inhibitor, as a novel therapeutic strategy for BTC. Our findings show that tazemetostat has anti-tumorigenic properties in BTC, with strong epigenetic effects.
Article
Biochemistry & Molecular Biology
Grace Tartaglia, Pyung Hun Park, Michael H. Alexander, Alexander Nystroem, Joel Rosenbloom, Andrew P. South
Summary: Junctional epidermolysis bullosa (JEB) is a skin disorder caused by a deficiency in genes associated with epidermal adhesion. Trametinib, a MEK inhibitor, can accelerate disease onset and decrease epidermal thickness in a mouse model of JEB. However, the adverse effects can be counteracted by the use of Losartan, an EB-anti-fibrotic drug.
Letter
Dermatology
Eva W. H. Korte, Phyllis Spuls, Peter C. van den Akker, Dimitra Kiritsi, Martin Laimer, Anna M. G. Pasmooij, Rainer Riedl, Elizabeth Vroom, Verena Wally, Tobias Welponer, Maria C. Bolling
Summary: The COSEB kick-off meeting in April 2023 emphasized the need for reasonable harmonization of outcome measurement in different types of epidermolysis bullosa (EB) through the development of core outcome sets. The standardized and uniform outcome assessment has the potential to reduce selective reporting, improve comparability and pooling of treatment outcomes, and enhance future research efficacy in EB.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Review
Cell Biology
Collin Y. Ewald, Alexander Nystroem
Summary: This article discusses the roles of hemidesmosomes in tissue regeneration and aging, and emphasizes the importance of dynamic mechanoregulation of hemidesmosomes in tissue maintenance and healthy aging.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Bernadette Liemberger, Johannes Bischof, Michael Ablinger, Stefan Hainzl, Eva M. Murauer, Nina Lackner, Patricia Ebner, Thomas Kocher, Alexander Nystroem, Verena Wally, Elisabeth Mayr, Christina Guttmann-Gruber, Josefina Pinon Hofbauer, Johann W. Bauer, Ulrich Koller
Summary: Mutations in the COL7A1 gene can cause skin problems by affecting type VII collagen (C7) in the basement membrane zone. The researchers used an RNA therapy called spliceosome-mediated RNA trans-splicing (SMaRT) to correct mutations in COL7A1. They successfully corrected mutations in RDEB keratinocytes and RDEB skin equivalents by introducing a repair molecule called RTM-S6m.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)