Epidermolysis Bullosa Orphan Disease By Annie Wibking

Epidermolysis Bullosa Genetically inherited Blistering of skin Minimal trauma to skin causes blisters and scarring

Types of epidermolysis bullosa (EB) Table 1 3 Number of subtypes Inheritance of subtypes Key genes affected EBS ~ 12 subtypes dominant or recessive Keratins 5, 14, Plectin JEB ~ 6 subtypes recessive Collagen XVII, Integrin, Laminin DEB ~ 13 subtypes Collagen VII

Autosomal Recessive Inheritance Recessive -> ¼ chance of EB Dominant -> ½ chance of EB Incidence -> 1 out of 50,000 births

How EB Affects the Skin Lack of proteins that cement epidermis to basement membrane and basement membrane to dermis Figure 1 10

Proteins involved in EB EBS – KRT-5, KRT-14, PLEC JEB – Laminin 5, Integrin, Collagen 17 DEB – Collagen 7

Dystrophic EB Most severe form of EB Scarring involved Fusion of digits -> “mitten hands”

Diagnosis of EB Family history Blistering of skin as an infant Skin biopsy read with transmission electron microscope Immuno-fluorescent antibody testing Molecular testing for genes involved (7)

Quality of Life - poor Pain Itching -> pain Disfigurement from scarring Dressing changes painful Most severe forms - life expectancy 1-30 years Financial burden – cost of dressings Risk of skin cancer high

Standard Treatment Decrease trauma to skin Keep wounds covered Treat infections Fe, Vit D, Zinc supplements OT, PT, psychological counseling Surgical treatments – C/section

Research needed for RDEB Risk of cancer 90% 1/3 of skin involved at any one time Pain equal to third degree burn

Bone marrow transplant Study at Mayo Clinic (2007-2009) Risk of chemo therapy and post implantation immuno suppression Reserved for worst cases of EB

Stem cell therapy Culture of epidermal stem cells Infected cells with genetically modified virus that had normal collagen 7 Sheets of epidermal cells grafted over wounds

Revertant genes – “natural” gene therapy Patches of skin in DEB patient were normal Converted cells from normal skin to stem cells -> differentiated to epidermal cells that produced collagen 7 Normal skin used to cover wounds

Living band-aid Umbilical cord blood platelet gel Amniotic membrane grafted to wounds Both worked, but did not lead to formation of collagen 7 Temporary fix

FCX-007 : genetically modified fibroblasts Use of viral vector to insert into patient Collagen gene expressed FCX-007 cells Now in phase 1 & 2 clinical trials

Intradermal injections Injections of fibroblast with collagen 7 protein Produced anchoring fibrils No human trials

The future Genetic counseling Preimplantation genetics Continued trials with stem cells and gene therapy Reduction of number of patients with RDEB and availability of better treatments

Registry for DEB DEBRA research facility and provides information to families Research on EB available at NIH Clinical Research Trials

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