For the first time ever, researchers have used gene therapy to correct the genetic defect and effectively ‘cure’ areas of skin in a patient with EB (Epidermolysis Bullosa).
The successful trial by Italian researchers has given hope to the 5,000 children and adults in the UK who live with this devastating and sometimes fatal condition in which the skin and internal linings blister at the slightest friction.
John Dart, director of DebRA, said that although the pioneering work was in the very early stages, it was a very exciting development in the fight against EB.
Mr Dart said: “This is one instance when the word breakthrough is not an exaggeration. This is proof of principle that gene therapy can work in the treatment of EB and it really does give hope to many families in the UK and across the world. It is now especially important that DebRA raises the money needed to commission research so that this treatment, developed by Italian researchers, can be explored and developed to benefit as many EB patients across the world as possible.”
Epidermolysis Bullosa literally means ‘blistering breakdown of skin’, and this happens because the skin lacks one type of protein that normally helps to hold the two layers together. The protein is defective because the gene which encodes it is also faulty.
The Italian team, led by Professor Michele de Luca at the University of Modena, has reported in the international journal Nature Medicine* that, by introducing a corrected copy of the gene into patches of badly affected skin of an EB patient, it has been possible to ‘cure’ these patches of skin: one year after treatment, the patches remain free of blisters, infections, and any inflammation or immune response. This work is the first proof-of-principle that a gene therapy might provide a solution to this otherwise incurable disease, and will give some hope to the hundreds of thousands of sufferers worldwide.
The gene therapy approach developed by De Luca and his team involved removing small patches of skin from the palm of the hand of the patient, a 36-year-old man with a type of EB known as JEB, or junctional EB. In JEB, the protein which is defective is called laminin. Epidermal skin stem cells from the patches of skin were grown in the laboratory, and correct copies of the laminin gene were inserted into the skin stem cells. [Epidermal stem cells are the cells in skin that are able to keep dividing to produce new epidermal cells and constantly renew our skin.] The corrected skin cells containing the laminin gene were then grown into sheets of skin in the laboratory, until they were of a size suitable for forming skin grafts.
The patient had badly affected areas of skin on the upper front part of his legs where the skin was extremely fragile, with non-healing wounds: these were the areas selected for grafting with corrected skin. The team removed the outer epidermal layer of the patient’s skin in these areas, and then grafted corrected skin onto four patches on one leg, and five patches on the other. Each patch was about 55 square centimetres, and a total skin area of 500 square centimetres was grafted.
The patient’s skin in these grafted areas had completely healed after one week and, a year later, these corrected areas of skin look normal and remain strong: they do not blister or itch even after being rubbed hard, although surrounding areas of uncorrected skin still blister even without any friction applied. Small samples of skin taken from grafted skin several months, and at a year, after transplant were examined under the microscope. This showed that the skin looked normal, and that the outer epidermis was firmly attached to the underlying dermis layer of the skin. With these initial promising results, De Luca’s team plans to continue with a systematic, stepwise replacement of other areas of this patient’s skin over the next two to three years.
This study shows for the first time that genetically corrected epidermal stem cells can be used to generate a functioning, self-renewing epidermis in patients, and the successful outcome of this clinical trial paves the way for gene therapy of other types of EB, as well as for some other genetic skin diseases.
DebRA UK manages research on behalf of an international consortium of national DebRA organisations with interests in furthering research.
Although DebRA UK did not fund this particular piece of research, it is currently working with Professor de Luca in the context of another EB gene therapy project, funded by the EU.
* “Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells” Nature Medicine Advance Online Publication; 19 November 2006
Notes for Editors
1. Epidermolysis Bullosa (EB) is a group of very rare genetic conditions in which the skin and internal body linings blister at the slightest trauma, causing painful wounds which fail to heal properly. It is an inherited condition (i.e. it is not infectious and cannot be ‘caught’), affecting 1 in 17,000 live births, leading to around 5,000 people affected in the UK, and around 500,000 worldwide.
EB is caused by genetic mistakes (mutations) in one or more of the genes for the proteins that are part of skin. In EB, faulty genes lead to faulty proteins, and therefore fragile skin. EB exists in three distinct forms, each with various subtypes, depending on which genes are affected: EB Simplex (EBS); Junctional EB (JEB); and Dystrophic EB (DEB). Some forms of EB are associated with an aggressive and usually fatal form of skin cancer. People with the more severe types of recessive dystrophic EB have an exceptionally high risk of developing such skin cancers, shortening their lives by approximately 30-40 years.
2. DebRA organisations exist in many countries and are charities working on behalf of people with the genetic skin blistering condition, Epidermolysis Bullosa (EB). DebRA funds research into EB to find the causes of, and treatments and cures for, this distressing disease. DebRA’s Research Priorities are in Genetics and Gene Therapy, Cancer in EB, Wound Healing, and Clinical research aimed at symptom relief.
DebRA UK [www.debra.org.uk] coordinates the research programmes of DebRA groups worldwide and facilitates close collaboration with the principal EB research teams worldwide.
