Ectodermal dysplasias caused by mutations in the p63 gene include the following:

AEC and EEC Research Overview

By Maranke Koster, Ph.D.
East Carolina University

AEC and EEC are ectodermal dysplasias caused by mutations in the p63 gene.  Although only AEC has historically been linked to the presence of skin erosion, data from the NFED’s Ectodermal Dysplasias International Registry indicate that over 25% of EEC patients exhibited skin erosions at some point during their lives.

Our overall goal is to develop a strategy for the treatment of skin erosion in AEC and EEC patients by generating healthy replacement skin that will not be immunologically rejected by the patients.  To accomplish this goal, we are developing a strategy that utilizes the patients’ own skin cells.

These cells will be temporarily transformed into immortal stem cells, termed induced pluripotent stem cells (iPSC).  After correcting the patients’ p63 mutation using modern gene correction tools, the iPSC will be directed to develop into healthy skin cells.  These cells are then used to generate full-thickness replacement skin for transplantation.

Since these cells originate from the patient receiving the transplant, immunological rejection of the skin grafts is unlikely.  Although it will take some time to make this treatment option a reality, we have already made significant progress.  This progress would have not been possible without the support of the NFED and willingness of its members to support our research by providing skin biopsies.

In addition, we plan to use the iPSC-derived skin cells (either with or without p63 mutation) to answer mechanistic questions about p63.  Examples of questions we aim to answer are: Why do certain mutations in p63 cause AEC whereas others cause EEC? Why do some EEC mutations cause skin erosions and others do not?

Are skin erosions in AEC patients similar to those that occur in a subset of EEC patients?  A better and more precise understanding of the role of mutant p63 proteins in both AEC and EEC may lead to the development of therapeutic options that are less invasive than the proposed cell therapy.

Experiments addressing both research objectives are performed simultaneously thereby increasing the possibility for developing novel therapies for skin erosions in AEC and EEC patients.  Further, very similar approaches can be used to develop therapies for corneal lesions.

For the latest update, read how Missing Proteins May Contribute to Skin Fragility in AEC Syndrome.