Protein Replacement Therapy
Protein replacement therapy attempts to replace or boost the protein that is defective or missing in individuals with EB through localized injections, micro-needle applications, and systemic therapy. Researchers at the University of Southern California (USC) and Stanford University continue to advance work in this area.
Simultaneously, Shire, a leading public pharmaceutical company, is working to commercialize protein replacement therapy for Dystrophic EB. EBRP has been a key funder of the work at both Stanford and USC and helped facilitate Shire’s interest and involvement with EB.
While not a cure, protein replacement therapy would be a “game changing”-treatment, allowing individuals with EB to have a better quality of life. Future research in this area could include investigating topical and ocular applications.
The theory behind cell therapy is that stem cells, fibroblasts, or gene-corrected cells can be injected locally or systemically, resulting in either temporary or permanent expression of the specific protein that is defective in individuals with EB.
In a notable cell therapy trial, doctors at the University of Minnesota have performed bone marrow transplants on individuals with RDEB and JEB, seeking to replace their bone marrow with a donor’s bone marrow that has the proper protein production capability. As the body’s wounds heal and the skin regenerates, the theory holds that the body will produce proper proteins for healthy skin.
At Kings College in the United Kingdom, in an on-going trial, researchers have yielded promising initial results by injecting fibroblasts into the skin of individuals with EB.
Academic institutions in the United States and commercial companies such as Fibrocell Science, Inc. are working on localized and systemic applications of gene-corrected cells, which would give many of the benefits individuals with EB have experienced from donor cells without the trauma of ablating a patient’s bone marrow.
Gene therapy consists of using methods to carry the correct gene into the patient’s cell, where the correct gene then causes the cell to make the correct protein. A localized form of gene therapy for individuals with RDEB is in clinical trials at Stanford University. In this trial, a small section of skin is removed from a person with RDEB, and the skin is grown in culture to form sheets of skin the size of playing cards. The correct gene is carried into the cultured skin cells by a virus. The corrected skin cells are then able to make the correct protein. The gene-corrected skin cells are then grafted back onto the body and the area of grafted skin is cured of EB. In Europe, similar human clinical trials are occurring for individuals suffering from JEB.
Stem cell therapy is another cutting-edge technique used to target the “error” in the gene that causes EB. In this form of treatment, an EB individual’s own cells are gene-edited ,then reintroduced into the body. Once corrected, the gene should express the correct protein, enabling the body to produce the missing protein, and EB is cured. Imagine a limitless and personalized supply of properly functioning cells as these corrected cells will reproduce and express the missing protein. Because the patient is receiving their own corrected cells, this is done without the risk of rejection that a bone marrow transplant presents. In addition, some forms of gene-editing are done without using a virus to correct the cell, which would also result in a safer form of gene therapy.
EBRP helped create and continues to support research enabling infrastructure to ensure that treatments will get to those in need as swiftly as possible. Key projects supported in this area include:
• The Epidermolysis Bullosa Clinical Research Consortium (EBCRC) was formed in 2011 to conduct clinical and translational research in EB and improve the lives of those suffering. The EBCRC is developing the infrastructure necessary to enhance collaborative multi-site clinical research and to secure funding for additional translational EB research. Current members of the EBCRC are leading physicians and researchers at Children's Hospital of San Antonio, Cincinnati's Children's Hospital Medical Center, Columbia University, Dell Children's Medical Center, Austin, Henry Ford Hospital in Detroit, Northwestern University, Phoenix Children's Hospital, Sainte-Justine Hospital University Center (Quebec), Stanford University, Toronto's Children's Hospital (SickKids), University of California San Diego, University of Colorado, University of Massachusetts, University of Miami, University of Minnesota, and Washington University.
• iScoreEB – Children’s Hospital of Colorado, in partnership with the Hospital for Sick Kids in Toronto, is developing an instrument for scoring clinical outcomes. As new therapies are developed, researchers will need a precise measure to see if the intervention improves the lives of EB patients. iScoreEB enables researchers to capture both clinically relevant and patient-reported outcomes in order to determine whether EB symptoms improve as a result of the intervention.