Stanford EB Research Update: May 2007

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:

Have a clinical diagnosis of RDEB by a local dermatologist
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
Are able to undergo adequate anesthesia to allow grafting procedures to take place
Both parents alive, do not have EB, and are willing to give consent for genetic testing.
Medically stable to travel to Stanford University Medical Center
No medical illnesses expected to complicate participation.
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.

Information about Epidermolysis Bullosa (EB)

Epidermolysis Bullosa (EB) is a rare, inherited, blistering skin disease that affects all ethnic and racial groups. There are several forms of EB ranging in severity from mild to lethal. Stanford University School of Medicine's Department of Dermatology has focused on EB research for the past 19 years. Our research is funded by the National Institutes of Health, the Epidermolysis Bullosa Medical Research Foundation (EBMRF) and the Nu Skin Force for Good Foundation. We have focused on identifying new strategies for the treatment of EB. These strategies have displayed promise at the pre-clinical levels in experimental models, and we are now ready to begin screening patients for possible gene transfer. For preliminary information about our research in EB see our Stanford EB Research Update: May 2007 and Stanford EB Research Update: February 2005.

We are working to develop a successful gene transfer for recessive dystrophic epidermolysis bullosa (RDEB) patients and are currently screening patients for the 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".

The process of developing a gene transfer trial in the United States of America is extremely complicated. Our major focus must be to minimize any risks that patients with RDEB would suffer in a trial. We are doing everything that we can to make this trial as safe as possible. The first required step is approval from the Recombinant DNA Advisory Committee (RAC). The RAC is a Federal Committee that considers the current state of knowledge regarding recombinant DNA. Since gene transfer involves use of recombinant DNA, the RAC review and approval is the very first step necessary for any human gene transfer trial in the USA. The RAC considers hypothetical hazards and methods for monitoring and minimizing risks. We received approval from the RAC on March 14, 2007. The webcast of that meeting is available here. [Scroll down the page to "Minutes and Webcasts", select "March 14, 2007" Webcast. Once loaded, fast-forward (move the slider bar) to approximately 4 hours and 38 minutes into the meeting, where our presentation begins. RealPlayer required].

We have had 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 involved continuous examination that our plans will minimize the risks that an RDEB patient, who enters such a trial, would face. We are currently screening for 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 currently screening subjects for possible gene transfer. We are in the process of trying to get the gene transfer trial approved by the proper regulatory agencies. In order to enroll in the study, once it is approved, you must first go through the screening process.

Who will be the first subjects in the trial?

The first subjects will need to be 18 years old or older, have RDEB, and be healthy enough to come to Stanford University for evaluation. It is possible that in the future we may be able to enroll subjects under the age of 18, starting with older age groups first. If this occurs, we will update this website with that information.

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.

Support EB Research at Stanford

Your support will help us accomplish our goal to ease the suffering of EB patients much sooner. To make a donation now, please click on the button below. If you wish to mail a donation, the addresses are listed below..

Stanford Department of Dermatology
Attn: Alfred Lane, MD
900 Blake Wilbur Drive
Stanford, CA 94305-5334

More information about donating

EB Medical Research Foundation
Northern California Office
130 Sandringham Road
Piedmont, CA 94611

Southern California Office
8909 W. Olympic Blvd., #22
Beverly Hills, CA 90211

More information about the EBMRF