Why do some people develop psoriatic disease and others don’t? The answer could lead to new ways to treat, cure or even prevent it, says Michael Siegel, Ph.D., senior vice president of research and clinical affairs at the National Psoriasis Foundation.
Researchers have known for some time that psoriatic disease has a genetics component. “Identical twins don’t always both get psoriasis, but they do both get psoriasis more often than fraternal twins or siblings; that tells us that there is an important role for genes,” says James T. Elder, M.D., of the University of Michigan’s Psoriasis Genetics Laboratory in Ann Arbor. But genetics is not the sole cause of psoriatic disease. As first shown by twin studies, other factors, including the environment, play a role as well, Elder says.
Scientists have been studying the genetic makeup of humans for years, achieving a major breakthrough in genetics research in 2003, when after 13 years scientists in 20 countries finished mapping all the genes in the human body, known as the Human Genome Project. The project provides researchers with a greater understanding of the body’s 25,000 protein-coding genes, including where each is located on chromosomes, the thread-like structures that package DNA, which determines an organism’s traits.
In the past, genetics research had been costly and time-consuming, even difficult, Siegel says. But advances in technology and computing power over the last two-plus decades have made it easier to do much more meaningful research, he says.
“We still have lots of questions remaining,” Siegel says. But as research methods have improved, researchers are developing a better understanding of what happens when someone develops diseases including psoriasis and psoriatic arthritis (PsA).
The increase in computing power and advances in technology have made it possible to collect a huge amount of data, and having extensive data is critical. “You may need thousands or even millions of samples to analyze to be able to come to meaningful conclusions,” Siegel says.
Data sources expanding
More than 25 years ago, when Elder began researching, his lab performed experiments measuring the tightly regulated process that allows a cell to respond to its changing environment, a process called gene expression. At that time, researchers measured the expression of five genes on 10 patients with psoriasis and 10 without. The slow, tedious process eventually led to 500 data points. Today, he says, his team is able to measure more than 1 million variants per person on tens of thousands of people. “It’s a totally different ballgame,” Elder says.
Because of the known genetics component, a great deal of psoriatic disease research focuses on DNA, which can be extracted from blood samples or obtained from cheek swabs and skin biopsies. Today’s researchers get DNA not only directly from physical samples volunteered by patients but also from patient registries and from direct-to-consumer genotyping companies such as 23andMe. By collaborating with 23andMe, Elder’s lab at the University of Michigan has increased its sample size by about 20 percent. This year, Michigan’s Psoriasis Genetics Lab is leading an international partnership that will increase its sample size by approximately 30 percent.
With NPF support, Elder and his colleague, Alex Tsoi, Ph.D., are collaborating with a team of Canadian researchers led by Dafna Gladman, M.D., to combine their genome sequencing studies, clinical data, electronic health record data and data from the Michigan Genomics Initiative at the University of Michigan to better predict which psoriatic patients will develop PsA. In addition, they are creating a panel of blood-derived biomarkers that identify normal biological processes to add to this data mix, further enhancing the ability to predict PsA.
The Michigan lab is looking not only at genetic triggers but also at environmental factors that may contribute to psoriatic disease. Elder says that even healthy skin is home to billions of microbial “fellow passengers” (known as the microbiome) and that one of these, a bacteria called streptococcus, is the cause of strep throat — a major trigger for guttate psoriasis.
Patients share experiences
Patients can’t conduct genetics research at home, but they can still help researchers by providing their own observations and experiences. In July 2015, NPF launched Citizen Pscientist, a global online research platform, to give people living with psoriatic disease the opportunity to contribute to psoriatic disease research. Community members, called “pscientists,” fill out online questionnaires about their symptoms, triggers, treatments, associated health conditions and lifestyle factors. “There are more than 75 questions that patients answer,” Siegel says. So far, more than 5,300 people have registered, and that number grows each day.
In December 2016, about 20 Citizen Pscientists and researchers met in Dallas to look at survey results from roughly 800 patients. They identified understanding the benefits and risks of home-based phototherapy as one of their top research priorities. As a result, in 2017, Joel Gelfand, M.D., a dermatologist at the University of Pennsylvania, received $8.6 million to study the effectiveness of phototherapy for psoriasis in a home-based versus office-based setting.
Patients also provide data through the Corrona Psoriasis Registry, which was developed in collaboration with NPF in 2015 and follows psoriasis patients under a dermatologist’s care. Two years earlier, Corrona, based in Waltham, Massachusetts, had launched a registry for people with PsA who are under the care of a rheumatologist.
Corrona’s registries don’t collect blood or serum samples; instead, they rely on questionnaires completed by health care providers and their patients. “The patients and dermatology providers complete questionnaires approximately every six months during routine outpatient visits,” says Jeff Greenberg, M.D., Corrona’s chief scientific officer.
This information is used to study such things as the safety and effectiveness of different treatments, he says. Scientists also use the data to examine the natural course of psoriasis and comorbidities – diseases such as diabetes or heart disease present in the same person.
“The NPF Medical Board and other leading dermatologists have the opportunity to collaborate with Corrona’s biostatisticians and epidemiologists to drive new insights in effectiveness and safety of different treatments,” Greenberg says. Pharmaceutical companies provide funding support to the registry and collaborate on research studies with Corrona.
Clinical trials provide safety data on treatments for a limited time period, Greenberg says. “Our registries collect real-world data, long-term, that can lead to a better understanding of safety profiles and improved treatment of patients with psoriatic disease,” he says.
The data keeps flowing
The Utah Psoriasis Initiative (UPI) at the University of Utah invites patients with psoriasis and PsA to help with research on genetics and its role in psoriasis; it also includes their family members and unaffected patients, who serve as controls. Kristina Callis Duffin, M.D., co-founded UPI in 2002 with Gerald Krueger, M.D. They also work with rheumatologist Jessica Walsh, M.D., on PsA. The initial intent was to use a unique genealogy database, the Utah Population Database (also at the University of Utah), to identify large families with a higher than normal occurrence of psoriatic disease.
“We have collected detailed clinical information, such as medical history, details about their psoriasis, a physical examination and blood from our volunteers,” says Duffin, a member of NPF's Medical Board. Sixteen years later, the UPI has more than 1,600 patients in its database — more than 1,300 who have psoriasis and about 250 who also have PsA.
UPI, in collaboration with the Michigan researchers, has used its data to examine which genes are associated with psoriasis and PsA, and what other comorbidities and associations people with psoriatic disease are likely to have, Duffin says. “Our intent is to generate hypotheses around what we find that will lead to studies of better treatments and possibly a cure for psoriasis and psoriatic arthritis,” she says.
The data also are being used to predict treatment outcomes and identify who, of those with psoriasis, might be likely to develop PsA. About 30 percent of people with psoriasis develop PsA, while some with PsA never get psoriasis.
NPF launched yet another source of data in 2006: The National Psoriasis Victor Henschel BioBank. Like the other labs, the BioBank was launched with the goal of finding what drives the onset and progression of psoriasis and PsA. “We hope to someday be able to say people with psoriasis have this specific genetic pattern and that it is some way responsible for or related to their psoriatic disease,” Siegel says. Currently, the BioBank includes samples from about 1,600 people with psoriatic disease and almost 1,400 without psoriatic disease.
Wiping out psoriatic disease
As researchers gather more data to better understand what triggers psoriatic disease in some people, they are getting closer to better, more individualized treatments. Early on, Siegel says, genetics research was “explorational, we had no idea what we were going to find.” Because researchers now have so much data, they are able to see patterns emerge and can begin to ask specific questions: Will someone with this genetic pattern be more likely to develop PsA? Will he or she respond better to this or that medication?
“We’re beginning to understand how proteins work with each other and how cells work with each other and how DNA plays a role in all of this,” Siegel adds. In the past, he says research was mostly the analysis of blood samples. Now that patients can provide information about their experiences through their smartphones or online, “we have a whole new kind of information that we can use to learn more.”
Patient data from Corrona and Citizen Pscientist and the like is extremely valuable, Siegel says. As research continues and data expands, the goal remains the same. “Ultimately, we hope that by understanding the fundamentals of the disease, we are able to predict what treatments patients are going to respond best to and ultimately leverage that into a cure.”
Privacy concerns respected
Some patients may be concerned about privacy and be reluctant to contribute personal information to these critical data banks, fearing the consequences if employers or insurance companies learn they have a risk of developing a progressive disease. Duffin says researchers recognize this concern.
“Investigators are very conscious of the need to protect patients’ protected health information and must adhere to ethical standards and data-sharing agreements when storing, analyzing and sharing patient data,” she says. Like all researchers, “we have consent forms that have detailed information about how we will use their information and how we protect their confidentiality.”
Elder notes that data can’t be collected without the patient’s consent. “In all cases, the patient must provide their informed consent for DNA and clinical data to be collected and analyzed,” he says.
Editor's note: This article originally appeared in the summer issue of Psoriasis Advance. Michael Siegel is now the former senior vice president of research and clinical affairs at NPF.
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