Researchers at King's College London have identified a new gene
(PIM1), which could be an effective target for innovative
treatments and therapies for the human autoimmune disease,
psoriasis.
Psoriasis affects around 2 per cent of people in the UK and
causes dry, red lesions on the skin which can become sore or itchy
and can have significant impact on the sufferer's quality of life.
It is thought that psoriasis is caused by a problem with the body's
immune system in which new skin cells are created too rapidly,
causing a build up of flaky patches on the skin's surface. It is
not known exactly why this problem occurs but it is thought that
certain genes may play a role.
The study highlights for the first time the role of PIM1 and the
IL-22 cytokine - a protein that sends messages between cells - in
skin inflammation such as that seen in psoriasis patients.
Scientists, led by Professor Frank Nestle from the St John's
Institute of Dermatology at Guy's and St Thomas' NHS Foundation
Trust and King's College London, injected IL-22 into models of
normal human skin in mice. The changes that subsequently occurred
in the skin were reminiscent of psoriasis. Injecting an antibody to
block the IL-22 cytokine caused these changes to reverse.
They were then able to perform computer analysis, comparing the
data from these human skin models with existing gene datasets, in
order to identify the gene PIM1 as one of the genes 'switched on'
by the presence of IL-22. They further showed that a small molecule
drug blocking PIM1 was effective in models of psoriasis. The link
between the IL-22 cytokine, which causes inflammation, and
subsequent changes in the PIM1 gene suggests a direct link between
PIM1 and psoriasis.
It is the first time that this gene has been identified as
having a specific link to the condition. The combined use of
computer analysis of complex gene data sets and disease relevant
human skin models, also called integrative biology, is innovative
and means that research can be more easily translated to further
clinical studies for patient benefit. This new type of approach
will likely generate more insights into disease mechanisms but also
new drugs for the treatment of psoriasis, thereby reducing the gap
between discovery and the clinic
Professor Nestle said: "We have been able to confirm that the
protein IL-22 causes inflammatory changes in human skin
contributing to psoriasis. The most exciting part of the study was
that detailed analysis of genes induced by IL-22 in skin allowed us
to uncover a novel treatment target for this disease. We are
hopeful that our research will lead to the development of new
approaches for the treatment for this common and irritating skin
condition."
The authors say that whilst this is a significant development
providing proof of principle in pre-clinical models of disease,
further research, in the form of clinical trials, is necessary in
order to test potential new treatments for effectiveness in humans.
However, as the findings are easily transferable to clinical
studies, the discovery of this new gene target has promise for the
development of new drug therapies.
The paper, Integrative Biology Approach Identifies Cytokine Targeting
Strategies for Psoriasis, is published in Science
Translational Medicine.