We are currently looking for subjects to participate in a preliminary screening for a possible gene transfer trial for recessive dystrophic epidermolysis bullosa (RDEB).

We are looking for subjects who meet the following criteria:

1- Have a clinical diagnosis of RDEB by a local dermatologist
2- Are 18 years of age or more and are willing to give consent. Estimated to have at least 100 to 200 cm2 areas of open erosions on the trunk or extremities
3- Are able to undergo adequate anesthesia to allow grafting procedures to take place
4- Both parents alive, do not have EB, and are willing to give consent for genetic testing
5- Medically stable to travel to Stanford University Medical Center
6- No medical illnesses expected to complicate participation
7- Currently this study is limited to residents in the USA

If you meet the above criteria, you may be eligible to come to Stanford University and participate in the screening phase of our trial.  The screening will involve skin biopsies, blood tests, and genetic testing.  We will pay the travel expenses related to this trial.

If you would like more information, or have any questions regarding our study and/or our eligibility criteria, please contact our Clinical Trial Coordinator, Emily Gorell, at (650) 725-4302 or at egorell@stanford.edu.  Emily can send you a copy of the informed consent and other documents related to this trial.

Our relentless effort has been the development of successful gene transfer for recessive dystrophic epidermolysis bullosa (RDEB) patients which eventually will lead to a clinical trial.  Children with RDEB are born lacking normal type VII collagen.  Children with RDEB develop a relentless, scarring EB subtype, which produces painful blisters and wounds on skin and mucous membranes.  The incidence of RDEB is estimated to be about 1 to 2 per 1,000,000 people. Current therapy for RDEB consists of only palliative wound care and there are no therapies available that alter the course or severity of this disease.  We have demonstrated in our research laboratories that genetically corrected RDEB keratinocytes (skin cells from the top layer of skin) engineered to express type VII collagen can correct human RDEB skin tissue grafted onto immune deficient mice, providing proof of concept for corrective molecular therapy for RDEB.  We now hope to eventually extend this approach to RDEB subjects by grafting the patient’s own genetically corrected RDEB keratinocytes back on to their wounds as is described below.  This technique is called gene transfer.  If it works successfully it would be called "gene therapy".

We have several more major steps to complete before a clinical trial can commence.  These steps require close collaboration between our research group and several regulatory agencies including the Federal Drug Administration (FDA), the Stanford Human Research Protection Program (IRB), and the Stanford Administrative Panel on Biosafety.  Each of these steps involve continuous examination that our plans will minimize the risks that an RDEB patient, who enters such a trial, would face. We are working to develop a Phase 1 clinical trial.  Phase 1 studies are designed to determine the metabolic and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on effectiveness.  The current trial design involves 1) biopsy of the skin of the subject with RDEB, 2) growth of their keratinocytes in culture, 3) insertion of the correct COL7A1 gene into these cells, and 4) grafting of genetically corrected keratinocytes onto the RDEB subject’s wounds.  We have preliminary data that transplantation of an RDEB patient’s own genetically engineered keratinocytes to the patient’s own wounds will restore normal type VII collagen expression in the skin of the RDEB subjects. The objective of this study is to achieve proof-of-concept for this general approach to cell-based gene therapy in humans and to set the stage for further therapeutic extension in RDEB.  The initial trial will involve small areas of skin on adults 18 years old or older with RDEB.  In the USA 18 years of age or older is considered the age when a person can make their own decisions about health care, and they can decide if they do or do not want to enter this type of trial. 

Questions About What Will Happen Next

When will this trial begin?

We are unsure about when we will be able to start this trial. We are working diligently to move this research forward as fast as possible.  We are sharing this information now not to give false hopes but to inform you of our plans and current success.  If we are able to start the trial, we will announce that information on this web page, and we will also send information to physicians interested in caring for patients with EB. 

Who will be the first subjects in the trial?

We hope to start to screen subjects for this trial in the near future.  Those subjects will need to be 18 years old or older, have RDEB, and be healthy enough to come to Stanford University for evaluation.  We need to obtain regulatory approval before we can begin screening.  There will be specific requirements that subjects must meet in order to make this trial as safe as possible for the potential candidates.  All of the requirements are not yet decided but will be considered by the regulatory agencies. 

Are there any risks with a gene transfer trial?

We are concerned about many risks. In one gene transfer trial for children with a lethal blood disease, several of the children developed leukemia.  In a previous trial for a metabolic disease, one child died.  In some of the trials for cancer some of the subjects have shown benefit and some have not benefited at all.  It is important to realize that a Phase 1 trial is designed to protect the subject while looking for any risks or illnesses that may develop.

What will happen next?

First will be the process of screening potential subjects 18 year old and older.  When that process starts we will put that information on this web page. 

RDEB affects infants and children. When can we try to help them?

Gene transfer trials of this type usually need to demonstrate benefit in adults before children can be tested.  If we are able to show benefit in adults with small risks, we will begin to test children as soon as possible.  We understand the pain and suffering that the children with RDEB feel.  We want to help as quickly.  We also do not want to do any experiments that may make the pain and suffering worse for children or adults.

Are we working on any other EB treatments?  

Yes, we are still examining the potential of protein therapy for EB.  In addition we continue to examine the relationship between RDEB and squamous cell carcinoma.  That information is in our Stanford EB Research Update: February 2005.

Is there someone I can speak to in order to understand more about EB, gene transfer, and cancer?

As in the case of therapy efforts, this web site is maintained to provide the most current public information on this subject and was designed to both inform the community and to prevent staff from being diverted from research efforts to repeat the same answers to similar questions arising from EB patient families around the world.  In the event that further information becomes available, this site will be updated to reflect this new information. Also your dermatologist who cares for you or your relative may be able to explain the details of this information to you.