How does the treatment work?
Small patches of skin were taken from the palm of the hand of the patient, a 36-year-old man with Junctional EB. Epidermal skin stem cells from the patches of skin were grown in the laboratory, and correct copies of the laminin gene (the protein that is defective in Junctional EB) 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 team removed the outer epidermal layer of the patient’s skin in these areas, on his legs 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 procedure was carried out under local anaesthetic.
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
Has this process been tried before?
Yes but until now it has not worked successfully. A very similar process was tried a few years ago with the same patient but the skin grafts failed to ‘take’.
What happens now?
The Italian research team will continue to work with the same patient, grafting additional areas of his body and continuing to monitor the graft sites.
Because EB is a rare condition, DebRA organisations from several countries are collaborating to recruit a further five or six patients who might be suitable to be treated in the same way.
Why will the trial be so small?
EB is a rare condition and this particular type of EB affects around ten percent of all patients with EB.
Of those patients, not all will be suitable for the trial and others will not want to take part.
This means that any trial involving treatments for EB will naturally involve a small number of people.
What are the limitations of this treatment?
This trial was successful on one patient with a particular type of EB. It may not be suitable for, or work for, other patients with JEB, which is why the trial needs to be widened. Also the treatment can only be used on areas of skin which can be grafted. Some skin surfaces such as the lining of the mouth and the rest of the gastrointestinal tract, which can also suffer damage in patients with EB, are difficult or impossible to graft successfully.
There are other research projects currently taking place that are investigating different approaches to gene therapy which might be used to treat the whole body, but this research is still at a very early stage.
Will this treatment have an effect through the genetic line to the patient’s children?
This potential therapy will correct the genes only in the treated parts of the skin for the patient who receives the skin grafts – genes in all untreated parts of the body remain unchanged. The correction cannot therefore be inherited, as the treatments does not correct the genes in the sperm or eggs, so the EB gene will be passed down to any children in the same way it would if the treatment had not taken place.
Is it possible to correct all damaged skin on the body?
In theory it should be possible to correct all the skin where grafting is possible (some sites, such as internal sites, are difficult or impossible to graft) but whether that is necessary for patients, or whether they would want to undergo so much treatment would have to be judged on an individual basis.
If corrected skin could be grafted between the fingers it could potentially save the use of the hands (many EB patients’ hands become damaged after repeated blistering and scarring, which causes the skin between fingers to fuse) and if the skin on the soles of the feet could be corrected then it could allow patients to walk without pain.
Why doesn’t the research focus on all types of EB?
This particular project used a patient with Junctional EB but other projects, including several funded by DebRA UK, are looking at using gene therapy to treat other types of EB.
Different types of EB are the result of faults in different genes, so each treatment has to be specifically designed to correct that particular fault.
DebRA is funding a project looking at Recessive Dystrophic EB, another severe form of EB, which we are expecting to go to clinical trials in the next few years.
DebRA is trying to build up an infrastructure which supports, encourages, guides and funds researchers into a concerted effort to bring about treatments for EB.
Did DebRA fund this work?
Not this particular project, although DebRA is working with Prof de Luca on another project. The plan to extend the trial of this work to another five or six patients involves collaboration with other research groups in Europe whose work DebRA does fund.
The work DebRA has been funding will certainly have had an influence on the worldwide body of knowledge that informed this project.
DebRA is involved in several large, international projects where many laboratories are collaborating to develop safe and effective gene therapy technology.
DebRA Italy is now going with Prof de Luca to see the Italian Ministry of Health in a bid to secure more funding so there’s a strong DebRA influence on the work.
Who would fund treatment for more patients?
Gene therapy will be expensive, especially where treatments are tailored to individual patients, rather then being ‘off the shelf’ treatments. In addition, treatments such as this one, involving skin grafting, have the costs of surgical treatment and patient care.
As with most types of complex treatment, costs per patient might be expected to decrease as technology develops, but it is unlikely ever to be cheap.
No figure has yet been put on the cost although it is likely to cost somewhere in the region of around £10,000 to £50,000.
Were the treatment to become available on a larger scale it is not yet known who would fund it, whether it would be funded on the NHS or not. DebRA would have to campaign hard to get state funding and would continue to fund work to refine treatment.
The cost of a successful gene therapy where the skin is ‘mended’ has to be balanced against the hospital and other treatment costs of looking after an EB patient with lifelong chronic wounds which need to be bandaged, and may become infected frequently.
It would then be important to compare how the cost of this treatment compares to the ongoing treatment usually throughout a patient’s life.
