Psoriasis genetics research yields discovery
People with psoriasis made it happen
From January/February 2004 Psoriasis Advance
First posted March 5, 2004
The dedication, personal and financial support of scientists, physicians and the Members of the National Psoriasis Foundation have resulted in what is likely one of the most significant findings in the history of psoriasis genetic research—the identification of three genes linked to the disease.
Anne M. Bowcock, Ph.D., of Washington University in St. Louis, and her colleagues have identified three genes on chromosome 17 that are involved in the development of psoriasis. The alterations leading to psoriasis are involved in fine regulation of these genes, and lead to subtle changes. The specific changes are still being worked out by Dr. Bowcock and her colleagues. Each of the three genes, which in turn regulate other genes and the proteins they make, is associated with the immune system, understood to be inappropriately activated in psoriasis. The findings were published in the December 2003 issue of the prestigious journal Nature Genetics, and there are reports that two other laboratories have already replicated some of Dr. Bowcock's findings, though no confirmations have been published to date.
"This advance in our scientific knowledge is part of an intricate web of factors that seems to determine who gets psoriasis and who does not," said Gerald G. Krueger, M.D., a professor of dermatology at the University of Utah Medical School in Salt Lake City and a member of the Psoriasis Foundation's Medical Board.
The groundbreaking research was made possible by the efforts of the Psoriasis Foundation, which created the National Psoriasis Tissue Bank and opened it in 1994. This tissue bank, built with blood samples from hundreds of families with psoriasis, provided the raw material that the Bowcock team analyzed in its discovery. The Tissue Bank was entirely funded with money donated by Foundation members.
"This is an achievement that every member of the Foundation can and should be very proud of--it happened because people with psoriasis got together and made it happen," says Gail M. Zimmerman, president and CEO of the Psoriasis Foundation. Indeed, Members of the Psoriasis Foundation have raised more than one million dollars in direct support of the Tissue Bank and of Dr. Bowcock's work, and more than two million dollars in total support of psoriasis genetics research.
How genes are discovered
Most researchers now believe that many genes are involved in causing psoriasis, and each gene may make only a small contribution to each person's susceptibility. In all, it is suspected that at least a handful of genes are involved in psoriasis. This has made finding the psoriasis disease genes very difficult.
To find more disease-related genes, researchers such as Dr. Bowcock and her team must first pinpoint areas of DNA containing genes using psoriasis families. Once the areas of linkage are narrowed to very specific stretches on a chromosome, researchers try to refine the locations of the genes with additional gene landmarks and patient samples. The great advantage of this approach is that it leads to the identification whose role in psoriasis was never suspected previously. The specific changes that lead to susceptibility are also unexpected. In Dr. Bowcock's study one of the changes alters the way a different gene of the immune system (RUNX1) regulates other genes.
Susceptibility to at least two other autoimmune diseases (rheumatoid arthritis and lupus erythematosus) have also been shown to be due to alterations of regulation of other genes by RUNX1. Hence this type of research opens up hitherto unsuspected pathways that might be very important for psoriasis treatment.
Research teams around the world are working to identify other psoriasis susceptibility genes thought to play a role in the disease, and several genes are expected to be identified in the months and years ahead, including one on chromosome 6.
Once genes have been discovered, there is still a great deal of work necessary to confirm the way in which the genes are involved in psoriasis, and how they work to produce the disease.
Research must move from pure genetic studies to biology, and confirmation of the expression, presence and activity of the genes in involved and uninvolved skin. The Psoriasis Foundation recently funded such follow-up research that the Bowcock team is doing to investigate the precise role in psoriasis played by the genes on chromosome 17.
"Over the next few years, researchers are going to identify a large number of psoriasis susceptibility genes," Dr. Bowcock said. "These will be important building blocks toward finding a cure in the future. In the meantime, the findings could help pharmaceutical and biotechnology companies craft the next generation of medications to treat the disease, and ultimately lead to more successful management of psoriasis."
"These are exciting findings, but we know there is much left to do. The Foundation and its members will continue to be committed to supporting cutting-edge research into the causes of this disease," says Zimmerman. "We know now that we can do it, and that our strategy, perseverance and dedication has paid off. Together, we'll take the next steps toward finding better treatments and an eventual cure for this disease."
A vision realized, fifteen years later
The journey began back in 1989, when the National Psoriasis Foundation gathered a group of international researchers for a workshop focused on identifying the most productive strategies for psoriasis research. The consensus of that group was that any meaningful progress toward an eventual cure for psoriasis would come from a thorough understanding of the genetics of the disease, and they recommended that the Foundation establish a large, centralized "bank" of psoriasis tissue, or blood, samples that researchers could use to study psoriasis genetics.
Approximately four years later, in 1994, the National Psoriasis Tissue Bank opened its doors. Researchers were quick to use it as a resource. Using data from the Tissue Bank, Anne Bowcock, Ph.D., and her team at the University of Texas Southwestern Medical Center, published an article in the prestigious journal Science that announced the first location of a suspected gene for psoriasis, on chromosome 17.
Dr. Bowcock dedicated herself and her laboratory to continuing the search, and her recent publication of the identification of three psoriasis genes in the journal Nature Genetics bears the results. According to Gail M. Zimmerman, President and CEO of the Psoriasis Foundation, "The psoriasis community is very lucky to have an expert geneticist of Dr. Bowcock's high caliber working on their disease, and the Foundation is grateful for her dedication and hard work."
Partially reprinted from the March/April 2002 Bulletin
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