SUMMARY OF RESEARCH BEING UNDERTAKEN
Epidermolysis Bullosa is a set of genetically inherited
conditions affecting 1 in at least 17,000 of the population. A fault in a gene causes the
skin to be extremely fragile. The layers of the skin do not adhere properly and painful
widespread blisters occur very easily. Currently there is no effective treatment. However
it is widely anticipated that gene therapy will eventually provide a cure for patients for
patients suffering from EB.
The goal of Gene Therapy has provided the impetus for much current research designed to
identify the spectrum of gene mutations responsible for the different subsets of EB, as
well as developing effective gene delivery strategies. DebRA recognises that this
reductionist (or "bottom-up") approach should continue to be complemented by the
reciprocal "top-down" strategy of devising novel means of promoting efficacious
would healing in EB patients. This latter approach is likely to be realised more quickly
than gene therapy and should therefore provide more immediate benefit to EB patients. With
this pragmatic objective in mind, the proposed study is concerned with learning more about
the basic cellular and molecular mechanisms involved in the control of normal wound
healing and how these may be beneficially manipulated in EB patients.
Summary of Research
The clinical management of EB patients is primarily concerned with the promotion of
wound healing. Unfortunately, this objective is not readily achievable with currently
available means and patients commonly suffer problems associated with persistent ulcers
and/or excessive scarring.
Normal wound healing proceeds through a series of stages which are tightly controlled
in their spatial and temporal sequence. The activation of connective tissue cells in the
tissue surrounding the wound is an early event following wounding and an essential
prerequisite for the induction of an effective healing response.
Prof Schor has identified and recently cloned a Migration
Stimulating Factor (MSF) which appears to play an important role in mediating this
process. MSF is constitutively expressed by connective tissue cells obtained by fetal
tissues (which exhibit rapid and regenerative
healing), is not expressed by normal adult fibrobalasts, but is transiently
re-expressed by cells at the wound site. Prof Schor has shown that MSF stimulates the
migration of connective tissue cells and their production of molecules known to promote
healing and reduce associated scarring. Interestingly, the precise nature of the
connective tissue molecules (such as collagen) in contact with these cells determines
their response to MSF, thus providing a mechanism for the control of its activity during
the wound healing process.
The objective of the proposed study is to compare connective tissue cells derived from
healthy donors and EB patients in terms of:
- their response to MSF with respect to directed cell migration and matrix biosynthesis,
and
- the manner in which this response is modulated by the extracellular matrix in contact
with these cells.
It is anticipated that these data will ultimately contribute to the development of the
next generation of wound dressings which will incorporate bioactive agents (such as MSF)
in conjunction with an appropriately modulating matrix support designed to activate tissue
cells and promote a (fetal-like) regenerative mode of healing. This work is very much in
the interests of people affected by the trauma of EB.
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