EBGene trial: Patient pre-selection outcomes for the European GENEGRAFT ex vivo phase I/II gene therapy trial for recessive dystrophic epidermolysis bullosa.

EBGene trial: Patient pre-selection outcomes for the European GENEGRAFT ex vivo phase I/II gene therapy trial for recessive dystrophic epidermolysis bullosa. Br J Dermatol. 2019 Sep 26;: Authors: Gaucher S, Lwin SM, Titeux M, Abdul-Wahab A, Pironon N, Izmiryan A, Miskinyte S, Ganier C, Duchatelet S, Mellerio JE, Bourrat E, McGrath JA, Hovnanian A Abstract Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin fragility disorder caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the major component of anchoring fibrils (AFs) that ensure dermal-epidermal adherence. From birth, RDEB patients endure lifelong skin and mucosal blistering with both local and systemic complications including aggressive metastatic squamous cell carcinomas (SCC).1 Currently, treatments are only symptomatic although clinical studies of novel therapeutics, including gene2 and cell3 therapies are emerging. One potential safety issue with such C7 replacement therapies, particularly in RDEB patients with null C7 expression, is the development of autoimmune EB aquisita caused by circulating neutralising autoantibodies against C7. PMID: 31557321 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research

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We report a 32-year-old man with RDEB with previously localized SCC who later developed metastatic SCC. He was started on cemiplimab (an immune checkpoint inhibitor) 350 mg IV every 3 weeks. An objective radiological response was noted within 3 cycles. On 14 months follow-up, there was a durable response to treatment clinically and on imaging, without immune-related adverse events. To our knowledge, this is the first case report describing safe administration of immune checkpoint inhibitors in a patient with RDEB with objective and durable response of metastatic SCC. Larger case series and controlled clinical trials are ne...
Source: Case Reports in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: Targeting TGFBR1 kinase activity may have therapeutic benefit in the majority of RDEB cSCCs, however, the potential tumour suppressive role of TGFβ signalling in a subset of RDEB cSCCs necessitates biomarker identification to enable patient stratification before clinical intervention. PMID: 32726455 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
This case report describes a woman in her 40s with recessive dystrophic epidermolysis bullosa and multiple cutaneous squamous cell carcinomas who was successfully treated with pembrolizumab.
Source: JAMA Dermatology - Category: Dermatology Source Type: research
Cutaneous squamous cell carcinomas (cSCC) are the primary cause of premature deaths in patients suffering from the rare skin-fragility disorder recessive dystrophic epidermolysis bullosa (RDEB), which is in ma...
Source: Cell Communication and Signaling - Category: Molecular Biology Authors: Tags: Research Source Type: research
Conclusions: There are many benefits to ATPSG reconstruction when chosen for the appropriate candidate. The meticulous technique and strict adherence to the postoperative protocol are crucial when these reconstructions are performed. Detailed descriptions of intraoperative and postoperative recommendations to optimize outcomes after ATPSG are presented.
Source: Plastic and Reconstructive Surgery Global Open - Category: Cosmetic Surgery Tags: Original Articles Source Type: research
Condition:   Recessive Dystrophic Epidermolysis Bullosa Intervention:   Sponsor:   Assistance Publique - Hôpitaux de Paris Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Dystrophic epidermolysis bullosa (DEB) is a hereditary skin fragility disorder, characterized by trauma-induced blistering followed by soft tissue fibrosis. One of the most feared complications is the early de...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Letter to the Editor Source Type: research
uml;m A Abstract Dystrophic epidermolysis bullosa (DEB) is a skin blistering disease caused by mutations in the COL7A1 gene encoding the anchoring fibril-constituent collagen VII.1 Secondary to skin fragility, DEB manifests as chronic wounds and progressive soft tissue fibrosis. As a consequence of a chronically injured and stiffened dermal microenvironment people with severe DEB are prone to develop early-onset metastatic cutaneous squamous cell carcinomas (cSCCs).1,2 Dermal fibrosis in DEB is paradigmatic of injury- and inflammation-driven activation of fibrogenic processes2 (and references therein). PMID: ...
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a devastating skin blistering disease for which there is still no available cure. Although RDEB is characterized by blisters caused by minimal trauma, non-healing wounds, recurrent infections, pseudosyndactyly, squamous cell carcinoma and others, one of the most challenging symptoms to treat in these patients is fibrosis. Healing takes place with an obvious scarring phenotype and RDEB can be viewed as a fibrotic disorder characterized by excessive ECM deposition, accumulation of collagen fibers, increase tissue stiffness and TGF β signaling.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research
Patients with epidermolysis bullosa (EB) require care of wounds that are often colonized with bacteria. A subset of EB patients are at risk for squamous cell carcinoma (SCC) and certain bacterial-host interactions have been implicated in this risk. The EB Clinical Characterization and Outcomes Database serves as a repository of information from EB patients at multiple centers in the US and Canada. Using this resource, we conducted a retrospective analysis of 739 wound culture results reported from 159 patients between 2001 and 2017 in the Research Electronic Data Capture Research Electronic Data Capture registry.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Genetic Disease, Gene Regulation and Gene Therapy Source Type: research
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