The Scleroderma Association of NSW Inc.
cannot offer direct advice on treatment or available therapies.
It is up to each patient to make all relevant health decisions
In consultation with their own doctor or health professional.
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1. New method of measuring gene expression from very small samples.
2. Further gene expression studies in Scleroderma and Morphea reveal a new family of genes
involved in endothelial cell inflammation. October 2004
3. Dr. Victor Chang's Research into Early Endothelin Antagonist Trial
in mildly symptomatic Pulmonary Hypertension patients.
The aim of this study has been to investigate the changes that occur on initiation of scleroderma. By understanding what is taking place on a cellular and molecular level we hope in the long term to reveal suitable targets of slowing down or even reversing the changes that occur in scleroderma. Early on in the project we decided to focus on morphea because it is possible to find morphea patients who are not on-medication (which might affect the changes we are trying to measure) and because the plaques (abnormal patch on the skin) have the property of advancing across the body. Our hypothesis had been that the changes that are occurring at the leading edge of these moving plaques might give a clue, as to what causes the skin to form plaques in both morphea and scleroderma. From a practical point of view, the plaques in morphea are also more clinically evident in diffuse scleroderma allowing us to compare diseased and unaffected areas in the same individual, thus giving us a perfect baseline for our measurements.
In the course of this research we have developed anew method of measuring gene
expression from very small samples. This allowed over 60 genes that are critical
in the pathways of inflammation and fibrosis to be measured in each biopsy
sample. In the future we think that we can extend this method to examine what is
happening in just a few selected cells using microdissection to cut out cells
out from a tissue biopsy. This will enable us to identify precisely where the
changes are occurring that we can measure.
When we compared the gene expression patterns between the diseased and
non-diseased areas of individual morphea patients, we found some genes were
consistently elevated at the edge of the plaque where the changes to tissue
structure are occurring. Some of these genes are characteristic of activated
fibroblasts (cell in connective tissue that synthesizes collagen) consistent
with the initiation of collagen synthesis in the skin. We also found genes that
are characteristic of macrophage cells. This might mean that macrophage
infiltration is an important early step in the initiation of skin disease. We
are currently using cell-type specific antibodies to see if we can confirm this
hypothesis using high powered microscopes.
We also
hope to be able to use specific antibodies to stain tissue sections for
compounds that we believe might be causing the changes to fibroblasts induced
actually happening when normal skin changes into
"scleroderma skin". This will be the first step to finding an effective way of
preventing or retarding the changes.
We
would like to take this opportunity of thanking the many supporters of the
Scleroderma Association of NSW for their generous support of this project.
Research always appears to proceed slowly as numerous hurdles have
to be overcome. We feel that our progress is now tangible and intend to carry on
the project through 2006. As a result we would like to continue to encourage
anyone with morphea or who has recently been diagnosed with scleroderma, and is
willing to help the project, to contact Wendy Gold at St Vincent's Hospital
on 8382 2820.
Please note -Now that "Scleroderma Australia"; (our new national Body) has
been established, we look forward to allocating (together with other States)
grants of research money Australia wide. Meanwhile Prof. Keith Stanley has
kindly offered to supply us with updates of his ongoing research at the Centre
for Immunology, St Vincent's Hospital.
October 2004 - Report from Professor K Stanley, Scleroderma Laboratory , St Vincent's Hospital
In the last report ( May 2004) we mentioned that inflammatory genes specific to endothelial cells were expressed in the tissue samples from morphea patients in areas where the skin had only been affected for a relatively short time. In contrast, these genes were not elevated in the scleroderma patients, probably because many blood capillaries are lost from the skin as a result of long-term scleroderma. We think therefore, that endothelial inflammation is an early process occurring in connective tissue disorders of the skin and possibly takes part in the development of scleroderma.
We were particularly interested to note that the novel gene family we previously found expressed in inflamed endothelial cells, was also highly expressed in the skin samples from morphea patients. Our recent activities have therefore included studies to elucidate the function of these genes (called NLF 1 and NLF2). So far we have shown that the proteins these genes encode are located in the nucleus of the cell, where DNA and other molecules that control the function of cells reside. The question is: what function do these NLF genes have?
We have used the latest in vitro molecular biology methods to design a small molecule to inhibit the expression of the NLF genes. We have tested this inhibitor and shown that it is effective in a simple test system. The challenge now is to use this tool to study the function of the NLF gene family in human endothelial cells. Preliminary data suggests that the NLF genes may control the shape of endothelial c-ells. Changes in cell shape are important during acute inflammation as they allow immune cells to migrate from the blood into peripheral tissue, by squeezing between endothelial cells. If the NLF genes are indeed involved in this process then the discovery will be very important. and could lead to possible treatments for inflammatory diseases. Although this work is at a very early stage, we are eagerly pursuing these experiments to find the answer.
Our research requires your participation to advance our understanding of inflammation in the development of connective: tissue disorders. If you have been diagnosed with scleroderma or morphea, and are interested in participating in our study, please contact Wendy Gold on 8382 2821 for more details.
For previous Australian research please go to our Archives
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The Scleroderma Association of NSW Inc.
cannot offer direct advice on treatment or available therapies.
It is up to each patient to make all relevant health decisions
In consultation with their own doctor or health professional.
Updated Updated Friday, 18. April 2008
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