Investigation of cell therapy for recessive dystrophic epidermolysis bullosa (RDEB) in Australia through intradermal injection of allogeneic fibroblasts.

INTERVENTION: Patients will have paired ulcers randomly treated with intradermal injection of cultured allogeneic fibroblasts (5 x10^6 per cm2) in a plasmalyte and 2% albumex solution. This will be performed during the baseline visit. Each paired ulcer site (placebo and treatment) will be treated with plasmalyte and 2% albumex solution injections or fibroblasts in a plasmalyte and 2% albumex solution. These paired sites will be injected at the same time or shortly after one another during the baseline visit. At 6 months, if the patient chooses to have the treatment sites re‐treated with fibroblast injections, then the opportunity will be provided for patients to have this performed. CONDITION: Recessive dystrophic epidermolysis bullosa PRIMARY OUTCOME: Primary outcome will be difference in area of the wound size from baseline to predetermined time points of the fibroblast injected wounds vs the placebo injected wounds. This will be achieved using the Visitrak wound measurement system [Smith & Nephew Healthcare Ltd., Hull]. Wounds will be serially measured for ulcer size and healing will be determined based on reduction in ulcer size from baseline measurements. To investigate the effect of cell therapy with cultured allogeneic fibroblasts on increasing the production of collagen VII in skin and restoration of normal skin electron microscopy ultrastructure (i.e. anchoring fibrils). Change in Col VII expression levels between base of ulcer at baseline and predetermined time points between the fibroblast injected ulcers and placebo injected ulcers. Collagen VII levels will determined via skin biopsies and direct immunofluorescence testing for collagen VII using LH7.2 and FNC1 antibodies to collagen VII. Anchoring fibril development will be determined via electron microscopy. SECONDARY OUTCOME: Change in Quality of Life score per patient over the time points. The tool used for this will be the Quality of Life in Epidermolysis Bullosa (QOLEB), an objective and disease specific measurement tool for measuring quality of life in patients with epidermolysis bullosa Change in appearance score of wounds for each treatment group as assessed by investigator and patient. The tool used for this will be the Visual Analogue Scale which provides a score from 1‐10 and the numbers will be evaluated over the time points from the subjects' and the investigator's perspective. Change in pain score of wounds for each treatment group. Change in pruritus score (VAS) of wounds for each treatment group. The tool used for this will be the Visual Analogue Scale which provides a pain score from 1‐10 and the numbers will be evaluated over the time points. Percent change in size of wounds for each treatment group. ; This will be achieved using the Visitrak wound measurement system [Smith & Nephew Healthcare Ltd., Hull]. Wounds will be serially measured for ulcer size and healing will be determined based on reduction in ulcer size from baseline measurements. Percentage reduction will be mathematically calculated uby comparing ulcer sizes at each time point with baseline values. INCLUSION CRITERIA: 1. Diagnosis of Recessive dystrophic epidermolysis bullosa‐ generalized severe (RDEB‐GS) (patients should have detectable low levels of collagen VII expression and reduced / abnormal anchoring fibrils on electron microscopy). 3. Ability to sign informed consent, which indicates the investigational nature of this study. 4. Age: 18 years or older 2. At least 2 symmetric wounds on each side of the body (arms, chest/abdomen, legs) of approximately the same size (at least 4 cm2 as measured accurately by the Visitrak wound measurement system [Smith & Nephew Healthcare Ltd., Hull]).