Picture Pac Man zipping across your video screen gobbling up dots. Now picture a Pac Man that moves inside the human body, munching away.
That’s how Dr. Chris Ritchlin, a rheumatologist at the University of Rochester in Rochester, New York, describes a cell called osteoclasts.
“They’re basically little Pac Men that chomp away at bone,” he said.
We all have osteoclasts. But, Ritchlin said, the progenitors of these cells—which are the cells that grow up to become osteoclasts—are greatly increased in people with psoriatic arthritis. That leads to bone loss in people with psoriatic arthritis over time.
Decades-long effort to study bone-chomping cells
Ritchlin discovered important information about how osteoclasts work in psoriatic arthritis patients thanks to two key grants from the National Psoriasis Foundation. In 1994, he received a $50,000 grant that helped him identify the type of cell—called monocytes—that are progenitors of osteoclasts. He found out that people with psoriatic arthritis have higher numbers of these cells.
“Those monocytes that were destined to become osteoclasts were greatly increased in psoriatic arthritis patients,” he said.
Ritchlin continued to study osteoclasts for years. Almost two decades later, in 2010, he received a two-year, $200,000 Translational Grant that helped him discover key information about how these cells work. He identified a molecule called DC-STAMP that plays a key role in the process that turns monocytes into bone-chomping osteoclasts.
NPF investment becomes multimillion dollar grant
Now, he’s turned his NPF funding into a five-year, $2.5 million grant from the National Institutes of Health (NIH) to learn more about DC-STAMP. What he finds out may eventually help doctors predict which treatments would work best for each individual patient.
The NIH grant will allow him to understand how DC-STAMP regulates the process that turns monocytes into osteoclasts, and learn more about how DC-STAMP affects bone loss and inflammation.
On top of that, Ritchlin is also going to use the NIH award to investigate how DC-STAMP may be used to predict a patient’s response to certain therapies.
Dr. Chris Ritchlin
Predicting how well a treatment works
Some biologic treatments for psoriatic disease, like Humira (adalimumab) and Enbrel (etanercept), target a specific cytokine, or pro-inflammatory protein, called tumor necrosis factor-alpha (TNF-alpha). But not every patient improves on these therapies. DC-STAMP may be useful as a biomarker that may help predict which class of drugs a patient will respond to and would be a major step forward, Ritchlin said.
Biomarkers are objective tests using blood, serum or other sources that doctors can measure to help them make decisions about diagnosis and treatment response.
DC-STAMP could be a useful early response biomarker to anti-TNF drugs, Ritchlin explained, because when some psoriatic arthritis patients are treated with these drugs, the cells that express DC-STAMP “drop very rapidly”— within two weeks.
When DC-STAMP levels drop, the process that turns monocytes into osteoclasts is disrupted, which halts bone loss.
Ritchlin’s team wants to find out whether the patients who experience this rapid drop in DC-STAMP after two weeks on the drug are the same patients who see significant improvement after four months. If so, he said, “This would be an early marker of treatment response, which we don’t have right now.”
With the biomarker as a guide, doctors would know right away to try a different drug in patients who did not see a rapid decrease in DC-STAMP.
“The idea is that if you don’t see a drop at two weeks, you would move to something else,” he said.
Ritchlin’s research could bring a test like this to patients and doctors in a couple of years, he said.
Diagnosing PsA before symptoms start
In the meantime, Ritchlin’s team is also working to determine whether DC-STAMP could be used as a diagnostic biomarker, predicting which people with psoriasis will go on to develop psoriatic arthritis.
The time it takes for a person with psoriasis to develop psoriatic arthritis is about eight to 10 years, Ritchlin said. He is studying whether testing to see if patients’ cells express DC-STAMP, along with power Doppler ultrasound imaging, can detect signs of psoriatic arthritis before it is clinically apparent.
A test using DC-STAMP that could warn patients about their risk for psoriatic arthritis and put them on the path toward systemic treatment earlier could mean that their arthritis might be improved or even prevented, he explained.
“We show that if you have psoriasis coupled with abnormalities on imaging, and elevation of DC-STAMP expressing cells and even in the absence of joint pain or inflammation that systemic treatment of psoriasis may have the potential to either lessen the severity or prevent the onset of the arthritis,” Ritchlin said.
Increasing federal dollars for psoriatic disease research
Ritchlin joins the growing group of NPF researchers who have won sizable NIH grants to research psoriatic disease. Increasing the amount of federal dollars for psoriatic disease research is one of NPF’s highest priorities. Grants from the NPF at the start of the project enable researchers to gather enough data to successfully apply for highly competitive NIH awards.
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