Update on EB research progress
Considerable progress is being made in the search for effective treatments for EB, with early stage clinical trials in progress or planned for several therapies. External funds are noticeably starting to come into the field.
Gene therapy:
In gene therapy the principle that it is possible was proved in 2006 when a single patient with Junctional EB was treated by grafting genetically modified skin onto his previously badly blistered thighs and long-term improvement was shown. Unfortunately, the mechanism used to modify the skin is now not allowed due to the development of cancers in some patients with another condition (unrelated to EB).
An alternative delivery mechanism is now being actively researched, both for Junctional and Recessive Dystrophic EB (RDEB). A five year programme, GENESKIN, funded by a European Commission grant of €4.9 million and in which DEBRA International is a partner, is focused on developing this therapy for RDEB with a Phase I clinical trial anticipated towards the end of the 5 year programme.
Cell therapy:
Cell therapies involve injecting live cells to the patient, with the goal of repairing, replacing or regenerating tissues or organs to restore normal function.
A Phase II clinical trial, funded by DEBRA, is in progress for a treatment which involves the infusion of fibroblasts (a constituent of skin cells) into patients with RDEB. Whilst not a cure, evidence so far suggests that it is likely to be effective in promoting faster wound healing, particularly in hard-to-heal wounds.
During 2011, Japanese/UK research has greatly increased the understanding of both what constituents of cells are involved in promoting wound healing and what how they are attracted to wound sites. The potential of mesenchymal stem cells (MSC) in wound healing is also becoming better understood. A trial of MSC therapy in RDEB, funded by the Sohana Fund (a dedicated fund for stem cell research within DEBRA raised by an affected EB family), is about to start.
In the USA two trials of bone marrow transplantation (BMT) are taking place at two sites. A systemic treatment, i.e. one which treats the whole body rather than local areas, such as BMT is a goal of EB therapy. At present, results are mixed and, sadly, there is a significant risk of death. Consequently, such trials are not planned currently in the UK. DEBRA International is, however, funding work at both US centres with the aim of trying to reduce risk and increase effectiveness.
Protein therapy:
Protein therapies involve injecting whichever protein is deficient into the patient. The human protein is made in the laboratory, synthesised from the human gene which has been cloned.
Laboratory work, particularly in the USA, has suggested that the injection/infusion of the defective protein in RDEB, type 7 collagen (COL7) may have a beneficial effect in promoting skin strength and wound healing. The research team at the University of Southern California has teamed up with a new company, Lotus Tissue Repair, to institute a $26 million programme to develop this form of therapy. DEBRA International has good contact with the research group and the company and plans to work closely with them.
Small molecule therapy:
In small molecule therapy for dominant forms of EB, particularly EB simplex (EBS), DEBRA is funding work to develop a drug-based therapy which will not be invasive and, ideally, be topically applied. It is hoped that an early clinical trial will be possible from 2013.
Skin cancer:
Tackling skin cancer in EB remains a research priority because, until it is possible to prevent the chronic wounds and scarring through reparative therapies, cancer continues to be a severe threat, particularly to those with RDEB. To identify possible ways of preventing or slowing cancer progression, the first step is to clarify the underlying causes, and DEBRA is therefore continuing to fund several research groups working on different aspects of the problem. Significant progress is being made in unravelling the various molecular and cellular mechanisms by which damaged EB skin is more prone to the initiation and spread of squamous cell carcinoma. What is promising is the increasing collaboration between the research groups who, by working on different parts of the jigsaw puzzle, are creating the full picture. In addition, some EB cancer research findings may be applicable to other cancers, and results are therefore attracting interest from other funders and industry - important partners in taking research through to the clinic.
As research moves ever closer to translating into therapy, DEBRA is focusing on how to manage the challenges of gaining market authorisation to get the therapies into the clinic and to persuade the NHS and other healthcare providers worldwide to pay for those treatments. Accordingly, relationships are being developed with industry, venture capital and regulators to help DEBRA through this process.