Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa

Rashidghamat, Ellie; McGrath, John A.

doi:10.5582/irdr.2017.01005

Cited by 94 publications

(88 citation statements)

References 146 publications

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“…The clinical scenario is variable from mild, localized disease, to generalized severe variants, that can be fatal in the first months of life . The phenotypic manifestations in DEB vary from mild autosomal dominant forms, with limited lesions, to severe autosomal recessive types . Different EB types and subtypes may also have different impact on patients’ HRQoL.…”

Section: Discussionmentioning

confidence: 99%

“…12,13 The phenotypic manifestations in DEB vary from mild autosomal dominant forms, with limited lesions, to severe autosomal recessive types. 14 10 However, some older children reported experience of avoidance by peers and bulling because of visible EB signs. 16 Normally, the impact of teasing and bulling in 3-4 years old children is even lower and absent in younger age 17 as we also detected during focus groups work.…”

Section: Discussionmentioning

confidence: 99%

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Epidermolysis bullosa‐specific module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire

Chernyshov

Suru

Gedeon³

et al. 2018

Acad Dermatol Venereol

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Background Epidermolysis bullosa (EB) may have severe impact on different aspects of patients’ life. Until now there was no EB‐specific quality of life (QoL) instrument for young children. Objective To create EB‐specific proxy module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire. Methods Focus groups with parents of children with EB were organized. Parents of EB children were interviewed by the project staff with regard to their perception of QoL issues of the skin disease of their children. Results Focus groups with parents of EB children in Ukraine and Romania were organized. Parents represented eight boys and 12 girls from 3 months to 4 years old with different EB types and disease severity. Based on the analysis of focus groups’ results, two EB specific items that were not mentioned by parents of children with other skin diseases and therefore were not included to the dermatology‐specific InToDermQoL questionnaire were developed: ‘problems with defecation’ and ‘problems with shoes’. These problems were mentioned by 55% of all parents and 11.76% of parents that represented EB children older than 1 year, respectively. Conclusion We want to invite other centres and EB related organizations to join our project starting from the pilot test. There are many different reasons why QoL measurement is important in dermatology clinical practice and our goal is practical use of the instrument in children with EB.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epidermolysis bullosa‐specific module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire

Chernyshov

Suru

Gedeon³

et al. 2018

Acad Dermatol Venereol

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“…These preliminary data suggest the potential effects of USSC administration on modulating dermal-cSCC microenvironment in patients with RDEB.Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin blistering disease caused by mutations in the COL7A1 gene that encodes type VII collagen (C7) [1][2][3]. Clinical manifestations of RDEB range from mild localized blistering to a severe generalized form (RDEB-sev gen; previously termed Hallopeau-Siemens subtype) characterized by erosions and blistering, mutilating scarring, pseudosyndactyly, and a high risk of developing aggressive and rapidly metastasizing cutaneous squamous cell carcinomas (cSCCs) [2][3][4].…”

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confidence: 99%

Cord Blood-Derived Stem Cells Suppress Fibrosis and May Prevent Malignant Progression in Recessive Dystrophic Epidermolysis Bullosa

et al. 2018

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Recessive dystrophic epidermolysis bullosa (RDEB) is a severe skin fragility disorder caused by mutations in the Col7a1 gene. Patients with RDEB suffer from recurrent erosions in skin and mucous membranes and have a high risk for developing cutaneous squamous cell carcinoma (cSCCs). TGFβ signaling has been associated with fibrosis and malignancy in RDEB. In this study, the activation of TGFβ signaling was demonstrated in col7a1−/− mice as early as a week after birth starting in the interdigital folds of the paws, accompanied by increased deposition of collagen fibrils and elevated dermal expression of matrix metalloproteinase (MMP)‐9 and MMP‐13. Furthermore, human cord blood‐derived unrestricted somatic stem cells (USSCs) that we previously demonstrated to significantly improve wound healing and prolong the survival of col7a1−/− mice showed the ability to suppress TGFβ signaling and MMP‐9 and MMP‐13 expression meanwhile upregulating anti‐fibrotic TGFβ3 and decorin. In parallel, we cocultured USSCs in a transwell with RDEB patient‐derived fibroblasts, keratinocytes, and cSCC, respectively. The patient‐derived cells were constitutively active for STAT, but not TGFβ signaling. Moreover, the levels of MMP‐9 and MMP‐13 were significantly elevated in the patient derived‐keratinocytes and cSCCs. Although USSC coculture did not inhibit STAT signaling, it significantly suppressed the secretion of MMP‐9 and MMP‐13, and interferon (IFN)‐γ from RDEB patient‐derived cells. Since epithelial expression of these MMPs is a biomarker of malignant transformation and correlates with the degree of tumor invasion, these results suggest a potential role for USSCs in mitigating epithelial malignancy, in addition to their anti‐inflammatory and anti‐fibrotic functions. Stem Cells 2018;36:1839–12

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“…Patients with RDEB suffer from recurrent erosions in the skin, oral mucosa, and gastrointestinal (GI) and genito‐urinary tracts . Moreover, patients with RDEB are at high risk of developing aggressive cutaneous squamous cell carcinomas, which is associated with a very poor prognosis . Currently, there is no cure for RDEB, other than supportive and palliative care.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, there is no cure for RDEB, other than supportive and palliative care. Nevertheless, significant progress has been made toward more effective treatment of patients with RDEB using a variety of approaches focusing on repair of genetic defects, protein replacement, and cell therapies .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Human Placental-Derived Stem Cells in Collagen VII Knockout (Recessive Dystrophic Epidermolysis Bullosa) Animal Model

Liao

Ivanova

Sivalenka³

et al. 2018

Stem Cells Translational Medicine

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Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating inherited skin blistering disease caused by mutations in the COL7A1 gene that encodes type VII collagen (C7), a major structural component of anchoring fibrils at the dermal‐epidermal junction (DEJ). We recently demonstrated that human cord blood‐derived unrestricted somatic stem cells promote wound healing and ameliorate the blistering phenotype in a RDEB (col7a1 −/−) mouse model. Here, we demonstrate significant therapeutic effect of a further novel stem cell product in RDEB, that is, human placental‐derived stem cells (HPDSCs), currently being used as human leukocyte antigen‐independent donor cells with allogeneic umbilical cord blood stem cell transplantation in patients with malignant and nonmalignant diseases. HPDSCs are isolated from full‐term placentas following saline perfusion, red blood cell depletion, and volume reduction. HPDSCs contain significantly higher level of both hematopoietic and nonhematopoietic stem and progenitor cells than cord blood and are low in T cell content. A single intrahepatic administration of HPDSCs significantly elongated the median life span of the col7a1 −/− mice from 2 to 7 days and an additional intrahepatic administration significantly extended the median life span to 18 days. We further demonstrated that after intrahepatic administration, HPDSCs engrafted short‐term in the organs affected by RDEB, that is, skin and gastrointestinal tract of col7a1 −/− mice, increased adhesion at the DEJ and deposited C7 even at 4 months after administration of HPDSCs, without inducing anti‐C7 antibodies. This study warrants future clinical investigation to determine the safety and efficacy of HPDSCs in patients with severe RDEB. stem cells translational medicine 2018;7:530–542

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Novel and emerging therapies in the treatment of recessive dystrophic epidermolysis bullosa

Cited by 94 publications

References 146 publications

Epidermolysis bullosa‐specific module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire

Epidermolysis bullosa‐specific module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire

Cord Blood-Derived Stem Cells Suppress Fibrosis and May Prevent Malignant Progression in Recessive Dystrophic Epidermolysis Bullosa

Efficacy of Human Placental-Derived Stem Cells in Collagen VII Knockout (Recessive Dystrophic Epidermolysis Bullosa) Animal Model

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