Pre-Clinical Studies to Date

Induced Pluripotent Stem Cells

We are continuing to explore potential treatments for EB patients. One such method is using induced pluripotent stem cells (iPSCs) for RDEB. This work is headed by Dr. Tony Oro and Dr. Marius Wernig. The goal of this project is to convert skin cells into stem cells, which will then be reprogrammed to correct the genetic mutation causing EB. These cells will then be turned into skin cells, which will be grown to form sheets of corrected skin, which will be grafted onto wounds. With our newly constructed Laboratory for Cell and Gene Medicine, manufacture of these sheets will represent a clinical-grade therapy, made according to the FDA’s current Good Manufacturing Practices (cGMP).

Stanford scientists are collaborating with Columbia University and University of Colorado, Denver on this project. This project is funded by EB Research Partnership and the California Institute of Regenerative Medicine. This study is still in the pre-clinical phase.

Pre-clinical results were described in the following paper:

Sebastiano, V, Zhen HH, Derafshi, BH, Bashkirova, L, Melo, S, Wang, P, Leung, T, Siprashvili, Tichy, A., Li,J, Ameen M., Hawkins, J., Lee, S., Li, L, Bauer, G., Lisowski, Kay, M., Kim, SK, Lane, AT, Wernig, M. and Oro, AE (2014) Corrected Induced Pleuripotent Stem Cell Based Therapy for the Treatment of Recessive Dystrophic Epidermolysis Bullosa. Sci Transl Med. Nov. 2014. 6:264-7.  Link to PubMed.

Other RDEB iPS cell links:

Blistering Skin Disease May Be Treatable With Therapeutic Reprogramming, Stanford Medicine

Link to Dr. Oro's Lab Site


Development of Gene Therapy

Before we were able to commence in-human trials of gene therapy for type VII collagen grafts, the scientists at Stanford Dermatology spent years doing research. They developed the retrovirus used to deliver the corrected type VII collagen to cells, perfected the method for growing the cells into sheets of skin, and performed mouse testing determine that it was safe to trial in humans. In a paper from Human Gene Therapy, they showed that this method was able to correct RDEB cells long term in mice. This paved the way for human clinical trials

Here are some references to key pre-clinical papers in the development of gene therapy (also known as gene transfer) for RDEB:

  • Siprashvili Z, Nguyen NT, Bezchinsky MY, Marinkovich MP, Lane AT, Khavari PA. Long term type VII collagen restoration to human epidermolysis bullosa skin tissue. Hum Gene Ther. Oct. 2010. 21(10):1299-310. Link to PubMed.
  • Ortiz-Urda S, Lin Q, Green CL, Keene DR, Marinkovich MP, Khavari PA. Injection of genetically engineered fibroblasts corrects regenerated human epidermolysis bullosa skin tissue. J Clin Invest. Jan. 2003. 111(2): 251-5. Link to PubMed.
  • Bauer EA, Herron GS, Marinkovich MP, Khavari PA, Lane AT. Gene therapy for a lethal genetic blistering disease: a status report. Trans Am Clin Climatol Assoc. 1999. 110:86-92. Link to Pub Med.


Protein Therapy

Stanford scientists are continuing to work on developing ways to treat RDEB using type VII collagen protein (which is the protein that doesn't work correctly in RDEB). 

Dr. M. Peter Marinkovich is leading these investigations.