1. Epidermolysis Bullosa
Orphan Disease By
Annie Wibking

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

3. 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

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

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

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

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

8. 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)

9. 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

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

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

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

13. 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

14. 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

15. 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

16. 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

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

18. 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

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

20. References
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8. Hovnanian A, et al. Exclusion of linkage between the collagenase gene and generalized recessive dystrophic epidermolysis bullosa phenotype. Journal of Clinical Investigation. 1991;88, [accessed 2017 Aug 1].
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19. Tolar J, et al. Patient-Specific Naturally Gene-Reverted Induced Pluripotent Stem Cells in Recessive Dystrophic Epidermolysis Bullosa. ScienceDirect. 2014;134(5) [accessed 2017 Aug 1].
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20. Vahlquis A. Epidermolysis bullosa. The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg Sep 19 [accessed 2017 Aug 1].
21. Wagner JE, et al. Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa. New England Journal of Medicine. 2010; 363: [accessed 2017 Aug 1]. Nevala-Plagemann C, et al.