Contrary to the prevailing professional opinion of the past few decades, recent experimental and clinical data support the fact that protein replacement therapy by allogeneic blood and marrow transplantation is not limited to freely diffusible molecules such as enzymes, but also large structural proteins such as collagens. A prime example is the cross-correction of type VII collagen deficiency in generalised severe recessive dystrophic epidermolysis bullosa, in which blood and marrow transplantation can attenuate the mucocutaneous manifestations of the disease and improve patients' quality of life. Although allogeneic blood and marrow transplantation can improve the integrity of the skin and mucous membranes, today's accomplishments are only the first steps on the long pathway to cure. Future strategies will be built on the lessons learned from these first transplant studies.
Bibliographical noteFunding Information:
This work was supported in part by grants from the National Institutes of Health (R01 AR063070 and R01AR059947), US Department of Defense (W81XWH-12-1-0609), Epidermolysis Bullosa Research Fund, Jackson Gabriel Silver Foundation, DEBRA, University of Minnesota Academic Health Center, Pioneering Unique Cures for Kids Foundation, Liao Family Fund, Sarah Moreland Fund, and the Children's Cancer Research Fund (Minneapolis, MN, USA). We could not have completed this work without the generous support of many people, but especially John A McGrath (St John's Institute of Dermatology, King's College, London, UK) who reviewed the results, challenged our assumptions, and provided a measure of objectivity to our interpretation of the data. We also thank Alain Hovnanian (Inserm U781, Imagine Institut, Necker Hospital for Sick Children, Paris, France) and Katsuto Tamai (Department of Dermatology, Osaka University, Osaka, Japan) who with McGrath reviewed every patient record to verify the appropriateness for enrolment onto the trial; Colleen Delaney, who continues to chair the Data Safety and Monitoring Board for this trial; Douglas R Keene (Microimaging Center at the Shriner's Hospital for Children, Portland, OR, USA) for doing nearly all the electron microscopic studies; Megan Riddle (University of Minnesota, MN, USA) for immunofluorescence imaging; and David Woodley and Mei Chen (Keck School of Medicine, University of Southern California, Los Angeles, CA, USA) for assessments of anti-C7 antibodies.