Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa

• Published in: The New England journal of medicine Vol. 363; no. 7; pp. 629 - 639
• Main Authors: Wagner, John E, Ishida-Yamamoto, Akemi, McGrath, John A, Hordinsky, Maria, Keene, Douglas R, Woodley, David T, Chen, Mei, Riddle, Megan J, Osborn, Mark J, Lund, Troy, Dolan, Michelle, Blazar, Bruce R, Tolar, Jakub
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 12-08-2010
• Subjects: Adolescent; Bone marrow; Bone Marrow Transplantation - adverse effects; Chemotherapy; Child; Child, Preschool; Collagen Type VII - genetics; Collagen Type VII - immunology; Collagen Type VII - metabolism; Collagen Type VII - ultrastructure; Epidermolysis Bullosa Dystrophica - genetics; Epidermolysis Bullosa Dystrophica - pathology; Epidermolysis Bullosa Dystrophica - therapy; Female; Fetal Blood - transplantation; Genes, Recessive; Graft Rejection; Humans; Male; Microscopy, Electron, Transmission; Mutation; Ostomy; Patients; Reticulin - ultrastructure; Skin; Skin - metabolism; Skin - pathology; Skin - ultrastructure; Stem cells; Transplantation Chimera; Transplantation Conditioning - adverse effects; Transplantation, Homologous; Transplants & implants
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa0910501

The use of marrow stem cells to treat seven children with severe epidermolysis bullosa caused by loss-of-function mutations in
COL7A,
the gene encoding type VII collagen (C7), was examined. The investigators observed increases in C7 deposition, the presence of donor cells in the skin, and an amelioration of symptoms.
Loss of skin integrity that leads to trauma-induced blisters and erosions is a defining feature of epidermolysis bullosa, a heterogeneous group of more than 20 inherited blistering diseases with highly variable clinical severity.
1
One of the most severe forms is recessive dystrophic epidermolysis bullosa, caused by loss-of-function mutations in the collagen type VII (C7) gene (
COL7A1
).
2
–
6
These mutations result in severely diminished expression of C7, a collagen localized at the dermal–epidermal junction. C7 is the major component of the anchoring fibrils that tether the epidermal basement membrane to the dermal matrix. In the absence of normal C7 . . .