RARE DISEASE
Severe generalized junctional epidermolysis bullosa
Severe generalized junctional epidermolysis bullosa
Severe generalized junctional epidermolysis bullosa
Synonyms: Epidermolysis bullosa letalis, JEB-H, Junctional epidermolysis bullosa generalisata gravis, Junctional epidermolysis bullosa, Herlitz type, Junctional epidermolysis bullosa, Herlitz-Pearson type, Severe generalized JEB
Synonyms: Epidermolysis bullosa letalis, JEB-H, Junctional epidermolysis bullosa generalisata gravis, Junctional epidermolysis bullosa, Herlitz type, Junctional epidermolysis bullosa, Herlitz-Pearson type, Severe generalized JEB
Synonyms: Epidermolysis bullosa letalis, JEB-H, Junctional epidermolysis bullosa generalisata gravis, Junctional epidermolysis bullosa, Herlitz type, Junctional epidermolysis bullosa, Herlitz-Pearson type, Severe generalized JEB
Drug discovery
0
drugs
With orphan designations
Overview
Severe generalized junctional epidermolysis bullosa (JEB) is a lethal autosomal recessive disorder characterized by profound skin and mucosal fragility, causing widespread blistering, chronic erosions, and exuberant granulation tissue. Key features include respiratory epithelial involvement, failure to thrive, and susceptibility to sepsis. Mortality exceeds 80% in infancy due to airway obstruction, malnutrition, or infection [1][10][14]. Caused by null mutations in LAMA3, LAMB3, or LAMC2 genes encoding laminin-332 [1][10].
Therapies
Wound care: Non-adhesive dressings (e.g., PolyMem®), antiseptics, and steroid creams for granulation tissue [12][18]
Systemic support: Nutritional supplementation (feeding tubes), IV antibiotics for sepsis, and airway management [3][12]
Emerging therapies: Phase III trials for ex vivo gene-corrected keratinocyte grafts and recombinant laminin-332 protein therapy [3][8]
Categories: rare developmental anomalies during embryogenesis, rare genetic diseases, rare odontological diseases, rare ophthalmic disorders, rare skin diseases
Research Papers
293 drug discovery papers related to Severe generalized junctional epidermolysis bullosa, with 4 first-in-class and 0 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
293 drug discovery papers related to Severe generalized junctional epidermolysis bullosa, with 4 first-in-class and 0 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-09 | Dermal papillary fibroblasts promote persistent granulation tissue formation in junctional epidermolysis bullosa.
The skin is composed of multiple fibroblast subpopulations with different functions in homeostasis and repair, but their role in skin diseases is largely unknown. Junctional epidermolysis bullosa (JEB) is a hereditary skin disorder characterised by severe skin fragility and aberrant granulation tissue formation, caused by loss-of-function variants in basement membrane proteins, including laminin-332. We developed JEB-like organotypic (OT) cultures with distinct fibroblast subpopulations and explored their role in an inducible JEB in vivo disease model, mimicking key features of the human disease. Mechanistically, papillary fibroblasts are highly increased in the granulation tissue of blistered JEB skin, promoting pathological αvβ6 integrin and TGFβ signalling in JEB keratinocytes. Treatment with the TGFβ receptor inhibitor RepSox not only normalised aberrant cell proliferation, differentiation, and cytokine signalling in JEB OTs but also reduced aberrant granulation tissue formation and skin blistering in laminin-332-depleted mice. Collectively, our study reveals that papillary fibroblasts promote JEB pathogenesis through increasing αvβ6 integrin and TGFβ signalling and disruption of these pathological signalling interactions significantly improved skin health and regeneration in JEB.
2026-06-25 | Wound-Healing Effects of Birch Bark and Propolis Extracts on Epidermolysis Bullosa Keratinocytes
Epidermolysis bullosa (EB) is a group of genetic diseases characterized by skin fragility. Although therapeutic options aim to accelerate wound-healing, improvement is needed; therefore, birch bark and propolis were investigated due to their beneficial biological properties. A representative ethanolic extract was analyzed by reversed-phase high-performance liquid chromatography with diode array detection (RP-HPLC-DAD) for chemical profiling of the raw materials. A hydrophobic natural deep eutectic solvent (HNaDES) for birch bark extraction, as well as a hydrogel and a bigel enriched with propolis and birch bark extract, were prepared and characterized by Fourier transform infrared (FT-IR) spectroscopy. Cytotoxicity and wound-healing potential were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch assays in six human keratinocyte cell lines: two from healthy individuals, two from recessive dystrophic ΕΒ patients (RDEB), and two from laminin-332-deficient junctional EB patients (JEB). RP-HPLC-DAD revealed the presence of phenolic compounds (e.g., chrysin, pinocembrin, pinobanksin) and pentacyclic triterpenes (e.g., betulin and betulinic acid), characteristic of propolis and birch bark, respectively. FT-IR confirmed HNaDES formation and indicated physical interactions within the gels. All systems exhibited no cytotoxicity at 1 μg/mL and increased cell vitality. Moreover, in keratinocytes derived from JEB patients, hydrogel improved wound- healing significantly at 24 h, whereas bigel showed significant improvement at 8 h. The developed systems could be promising topical treatments.
2026-06-23 | FP14 Recombinant protein therapy for the treatment of junctional epidermolysis bullosa
Abstract Introduction and aims Junctional epidermolysis bullosa (JEB) is a rare genetic skin disorder leading to severe skin fragility from birth. It is caused by mutations in genes encoding the skin basement membrane proteins, Laminin 332, type XVII collagen or the basement membrane binding integrin α6β4, which anchor the epidermis to the dermis. JEB is characterized by widespread blistering of the skin and mucous membranes. The most severe form, JEB generalized severe, is caused by loss-of-function mutations in one of the chains of the trimeric protein Laminin 332. Babies diagnosed with this form of JEB generally do not survive beyond their first birthday. Patients suffer from failure to thrive, poor wound healing, anaemia, respiratory complications, and infections. The aim of this project is to explore the possibility of delivering recombinant laminin 332 (rLM332) to JEB skin to improve skin function. Methods We used a tamoxifen inducible mouse model of JEB (Lama3flox/floxK14CreERT), in which the Lama3 gene is specifically deleted in K14 expressing cells. JEB mice develop progressive blistering of skin and mucosa and exhibit reduced weight gain, mirroring the human disease. We examined the potential of rLM332 to treat JEB, exploring topical and subcutaneous injection and the impact on wound healing and disease severity biomarkers. Results We found both subcutaneous injection and topical application of rLM332 results in localization of the protein to the basement membrane. We observed improved wound healing, reduced blistering, improved basement membrane type VII collagen localization, and changes to the immune environment with rLM332 treatment. These changes persist at least 10 days following the final application. Conclusions Recombinant protein therapy presents a promising avenue for the treatment of JEB in patients, with topical application a potential noninvasive method of delivery in babies with extremely fragile skin. Murine experiments indicate durable improvements in skin health and accelerated wound healing.
2026-07-09 | Dermal papillary fibroblasts promote persistent granulation tissue formation in junctional epidermolysis bullosa.
The skin is composed of multiple fibroblast subpopulations with different functions in homeostasis and repair, but their role in skin diseases is largely unknown. Junctional epidermolysis bullosa (JEB) is a hereditary skin disorder characterised by severe skin fragility and aberrant granulation tissue formation, caused by loss-of-function variants in basement membrane proteins, including laminin-332. We developed JEB-like organotypic (OT) cultures with distinct fibroblast subpopulations and explored their role in an inducible JEB in vivo disease model, mimicking key features of the human disease. Mechanistically, papillary fibroblasts are highly increased in the granulation tissue of blistered JEB skin, promoting pathological αvβ6 integrin and TGFβ signalling in JEB keratinocytes. Treatment with the TGFβ receptor inhibitor RepSox not only normalised aberrant cell proliferation, differentiation, and cytokine signalling in JEB OTs but also reduced aberrant granulation tissue formation and skin blistering in laminin-332-depleted mice. Collectively, our study reveals that papillary fibroblasts promote JEB pathogenesis through increasing αvβ6 integrin and TGFβ signalling and disruption of these pathological signalling interactions significantly improved skin health and regeneration in JEB.
2026-06-25 | Wound-Healing Effects of Birch Bark and Propolis Extracts on Epidermolysis Bullosa Keratinocytes
Epidermolysis bullosa (EB) is a group of genetic diseases characterized by skin fragility. Although therapeutic options aim to accelerate wound-healing, improvement is needed; therefore, birch bark and propolis were investigated due to their beneficial biological properties. A representative ethanolic extract was analyzed by reversed-phase high-performance liquid chromatography with diode array detection (RP-HPLC-DAD) for chemical profiling of the raw materials. A hydrophobic natural deep eutectic solvent (HNaDES) for birch bark extraction, as well as a hydrogel and a bigel enriched with propolis and birch bark extract, were prepared and characterized by Fourier transform infrared (FT-IR) spectroscopy. Cytotoxicity and wound-healing potential were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch assays in six human keratinocyte cell lines: two from healthy individuals, two from recessive dystrophic ΕΒ patients (RDEB), and two from laminin-332-deficient junctional EB patients (JEB). RP-HPLC-DAD revealed the presence of phenolic compounds (e.g., chrysin, pinocembrin, pinobanksin) and pentacyclic triterpenes (e.g., betulin and betulinic acid), characteristic of propolis and birch bark, respectively. FT-IR confirmed HNaDES formation and indicated physical interactions within the gels. All systems exhibited no cytotoxicity at 1 μg/mL and increased cell vitality. Moreover, in keratinocytes derived from JEB patients, hydrogel improved wound- healing significantly at 24 h, whereas bigel showed significant improvement at 8 h. The developed systems could be promising topical treatments.
2026-06-23 | FP14 Recombinant protein therapy for the treatment of junctional epidermolysis bullosa
Abstract Introduction and aims Junctional epidermolysis bullosa (JEB) is a rare genetic skin disorder leading to severe skin fragility from birth. It is caused by mutations in genes encoding the skin basement membrane proteins, Laminin 332, type XVII collagen or the basement membrane binding integrin α6β4, which anchor the epidermis to the dermis. JEB is characterized by widespread blistering of the skin and mucous membranes. The most severe form, JEB generalized severe, is caused by loss-of-function mutations in one of the chains of the trimeric protein Laminin 332. Babies diagnosed with this form of JEB generally do not survive beyond their first birthday. Patients suffer from failure to thrive, poor wound healing, anaemia, respiratory complications, and infections. The aim of this project is to explore the possibility of delivering recombinant laminin 332 (rLM332) to JEB skin to improve skin function. Methods We used a tamoxifen inducible mouse model of JEB (Lama3flox/floxK14CreERT), in which the Lama3 gene is specifically deleted in K14 expressing cells. JEB mice develop progressive blistering of skin and mucosa and exhibit reduced weight gain, mirroring the human disease. We examined the potential of rLM332 to treat JEB, exploring topical and subcutaneous injection and the impact on wound healing and disease severity biomarkers. Results We found both subcutaneous injection and topical application of rLM332 results in localization of the protein to the basement membrane. We observed improved wound healing, reduced blistering, improved basement membrane type VII collagen localization, and changes to the immune environment with rLM332 treatment. These changes persist at least 10 days following the final application. Conclusions Recombinant protein therapy presents a promising avenue for the treatment of JEB in patients, with topical application a potential noninvasive method of delivery in babies with extremely fragile skin. Murine experiments indicate durable improvements in skin health and accelerated wound healing.
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