Psoriasis research: From the inside out
From November/December 2005 Psoriasis Advance
Understanding psoriasis is an active area of scientific research. Current areas of emphasis include genetics, mechanism of disease, clinical research and burden of disease. In this article we will examine each of these areas of research, including why these areas are important to study and what is happening within each area.
Psoriasis genetics
Genetics is the study of our genes, the blueprint of who we are. Studying psoriasis genetics helps us understand who is susceptible to, or who will develop, psoriasis. Scientists believe that many people have the genes that lead to psoriasis, but not everyone who has these genes develops psoriasis. Once scientists identify psoriasis genes, they can study the genes further to understand the psoriasis mechanism of disease, or how psoriasis develops. A better understanding of how psoriasis develops and progresses will help scientists design treatments that target psoriasis and may lead to a cure.
Scientists believe that more than one gene is involved in psoriasis susceptibility, but genes do not tell the whole story. Environmental triggers play an important role in the development of this complex disease.
Scientists believe that as many as 20 regions of chromosomes are involved in psoriasis development. Scientists have focused on a region on chromosome 17 called PSORS2, and much progress has been made in understanding its role in psoriasis. Scientists are also studying a region on chromosome 6 called PSORS1; the region contains at least three candidate genes for psoriasis susceptibility.
Mechanism of disease
Once candidate psoriasis genes are identified, scientists can study these genes to understand how they function within the body and how this function may be altered during psoriasis. This area of
research, called "mechanism of disease," includes the study of skin (keratinocyte) biology, immunology (the study of the immune system) and animal models. By understanding the driving factors in psoriasis, from the genes to the skin to the immune system, researchers will be equipped with more knowledge and better able to develop targeted treatments.
Scientists once believed that psoriasis was caused by defects in skin cells but now recognize the importance of the immune system in psoriasis development. Researchers at Case Western University in Cleveland, Ohio, recently published a paper in the Journal of Immunology identifying a specific T cell that is altered (does not function normally) in psoriasis. Scientists are also beginning to understand the importance of another immune cell, the plasmacytoid predendritic cell (PDC), in psoriasis development. Researchers at the University Hospital of Zurich in Zurich, Switzerland, recently published a paper in the Journal of Experimental Medicine indicating the plasmacytoid predendritic cell can cause psoriasis to develop under specific conditions.
Animal models are also increasing our understanding of psoriasis, including the human-xenograft model (in the September/October 2005 Psoriasis Advance) and the Stat3 transgenic mouse (in the March/April 2005 Psoriasis Advance). A recent study in Nature by researchers in Vienna, Austria, describes a new psoriasis mouse model created by the deletion of specific proteins in the skin. This mouse also develops an arthritis that resembles psoriatic arthritis.
With the advent of biologics—drugs which are based on compounds found in living cells—researchers are now able to use these targeted drugs to understand the mechanism of disease. Researchers at Robert Wood Johnson Medical School in New Jersey and Rockefeller University in New York recently published a study in the Journal of Immunology showing that the TNF-inhibitor Enbrel (generic name etanercept) can decrease the expression of cytokines (chemical messengers in the immune system) responsible for skin inflammation in psoriasis. Researchers are also studying other biologics and how they affect psoriasis development.
Clinical research
The development of new, safe and effective treatments for psoriasis is critical to improving care for this chronic disease. Clinical trials have distinct phases to test different aspects of the drug. Phase I tests if the drug is safe. Phase II tests if the drug works (efficacy). Phase III is the continued study of safety and efficacy. (For more information on clinical trials, see the March/April 2005 Psoriasis Advance).
Scientists at the 66th annual meeting of the Society for Investigative Dermatology recently
reported the phase II results of CNTO 1275, a molecule that inhibits the cytokines IL-12 and IL-23. With one injection of CNTO 1275, more than 50 percent of participants achieved 75 percent or greater improvement in psoriasis 12 weeks after treatment. When the dose was increased and given once per week for four weeks, more than 80 percent of participants achieved 75 percent or greater improvement.
There are currently phase III trials for Humira (generic name adalimumab) and Remicade (generic name infliximab) in psoriasis. Extended safety and efficacy trials have been completed for Raptiva (generic name efalizumab) and are ongoing for Enbrel. Combination therapy is also generating much interest with trials for Amevive (generic name alefacept) with ultraviolet light B (UVB); Enbrel with psoralen plus UVA (PUVA); and Soriatane (generic name acitretin) with UVB.
Burden of disease research
It is important to quantify the impact of chronic disease. This data can then be used to educate doctors, insurance payors, legislators, media and the public about the impact of psoriasis and psoriatic arthritis.
The Psoriasis Foundation is conducting research in this area. The 2001 National Psoriasis Foundation Benchmark Survey collected a wide variety of valuable data, including the following highlights: Psoriasis is common (2.2 percent of American adults have been diagnosed with psoriasis); psoriasis carries a substantial burden; and Members of the National Psoriasis Foundation are more informed about treatment options. The Psoriasis Foundation continues to conduct research on the impact of disease.
Scientists are making breakthroughs at an unprecedented rate. As our understanding increases,
there is the potential of developing new targeted treatments. This is a time of great excitement and hope for the psoriasis and psoriatic arthritis community.
Research spotlight: James G. Krueger
James G. Krueger, M.D., Ph.D., of Rockefeller University in New York, is one of the top experts
in psoriasis research—focusing specifically on the mechanism of disease, or how the genes that are involved in psoriasis development and the immune system lead to its symptoms on the skin.
Like many researchers roughly 20 years ago, Dr. Krueger thought that psoriasis had no systemic
component. Now, due to the work of researchers like Dr. Krueger, psoriasis is known to start beneath the skin's surface in the immune system. He has published numerous papers in research journals on the mechanism of disease of psoriasis and new treatments for the disease. Much remains to be discovered, however.
"We probably understand about 20 percent of this disease," says Dr. Krueger. His lab focuses on understanding the cellular makeup of the disease, using targeted treatments to understand the disease and learning how the drugs work on the immune system.
"We seek to have an integrated understanding of psoriasis," says Dr. Krueger. "From that basis, we can go out and rationally try a new therapeutic," which may be safer and more effective long term. For example, Dr. Krueger was involved in identifying the expression of cytokine IL-23, a chemical messenger which may potentially be a target for new treatments.
Dr. Krueger also recently collaborated with other psoriasis experts, including Alice Gottlieb, M.D., Ph.D., in a study published in the August 2005 Journal of Immunology showing how Enbrel (generic name etanercept) decreases the chemical messengers responsible for psoriasis. This research helps to show how psoriasis is "turned off," and also provides insight into how biologics and other new treatments work.
More research is needed, and Dr. Krueger and other researchers call on the psoriasis community
to advocate on behalf of psoriasis research funding. More funding for psoriasis research, Dr. Krueger emphasizes, "will require advocacy on the part of patients and advocacy organizations, to say 'The disease is important to us.'"
Dr. Krueger also believes it's important for patients to become involved in clinical research
trials, which enable researchers to find safer treatments based on the cause of the disease. "It's really a partnership between the psoriasis patient and the researcher."
For more information on clinical trials, go to www.psoriasis.org/research/trials |
The National Psoriasis Foundation is advancing psoriasis research
The National Psoriasis Foundation is providing resources, awarding competitive seed grants,
conducting studies on the burden of disease and building collaborations to advance psoriasis
research.
Providing resources for genetics research
The National Psoriasis BioBank is a resource for psoriasis researchers. Using this collection of genetic samples with associated clinical information, researchers will follow people with
psoriasis over time (prospectively). Because psoriasis can change, this collection will provide
researchers information about the symptoms of psoriasis at specific points in time. The National Psoriasis BioBank is a component of the Genetic Alliance BioBank, a centralized biological and data repository that encourages cross-disease research. We will be telling you more about this important resource in the coming months.
Awarding grants to stimulate research
The Psoriasis Foundation has awarded more than $3.5 million in research grants. Our grant funding program is focused on genetics, immunology (study of the immune system) or clinical research focused on mechanism of disease. Our current seed grant program is designed to provide scientists with funding to generate preliminary data. This data can be used in National Institutes of Health (NIH) grant submissions to leverage more funding.
Conducting research on the burden of disease
The Psoriasis Foundation conducts research on the burden of psoriasis and psoriatic arthritis.
These studies focus on these diseases' impact on quality of life, treatment awareness and satisfaction, and impact on work productivity. This data is used to educate medical professionals, insurance providers, legislators and the media.
Building collaborations worldwide
The Psoriasis Foundation is building networks of medical and scientific professionals. The
National Psoriasis Foundation Medical Board is a talented group of medical professionals who focus on critical issues. The Psoriasis Foundation held the 8th International Psoriasis Genetics Committee Meeting in April 2005. This dynamic scientific meeting included more than 20 presenters and nearly 60 attendees from international laboratories.
The Psoriasis Foundation funds the International PSORS1 Genetics Consortium, a group working to identify the smallest segment in PSORS1, which is a region on chromosome 6 that may determine who develops psoriasis.
In these ways, the Psoriasis Foundation is truly taking an active role in advancing research. We are confident that our resources and forward thinking will generate an improved understanding
of psoriasis and psoriatic arthritis.
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