Targeting the immune system to find
better psoriasis treatments
By Nicole Van Hoey, Pharm.D.
In 2011, two psoriasis researchers—Dr. Peter Marinkovich of Stanford, Calif., and Dr. Antonio Costanzo of Rome, Italy— received National Psoriasis Foundation Translational Grants, which fund research that “translates” laboratory discoveries into treatments for psoriatic diseases. Each researcher received a two-year, $100,000 grant. Here is an update of their work at the end of their first year.
The immune response
Dr. Costanzo is an assistant dermatology professor at Rome’s Tor Vergata University, where he helps conduct clinical trials. His interest in psoriasis research developed from interactions with patients and from growth in the fields of biologic treatment and early disease development.
With a background in both the immune system and skin diseases, Costanzo is studying how the immune system triggers new psoriasis plaques, especially when plaques start at a skin cut or scrape, a phenomenon called the Koebner effect. In his dermatology lab, Costanzo and his team are hoping to develop new psoriasis treatments by identifying substances found in skin wounds that trigger new plaques.
With a background in both the immune system and skin diseases, Costanzo is studying how the immune system triggers new psoriasis plaques…
In early research, Costanzo confirmed that substances called antimicrobial peptides, or AMPs, are released in cells when skin is injured. AMPs normally protect skin cells from infections after a cut. In people with psoriasis, however AMPs remain at the injury and trigger active new plaques there. Costanzo connected the amount of one particular AMP—LL37—in psoriasis skin cells with more severe psoriasis symptoms. LL37 may be an important new target for disease prevention, Costanzo says.
The researcher and his team are also studying the immune-system protein interleukin-21 (IL-21). Thick skin and extra skin cells—two hallmarks of psoriasis plaque formation—occur when IL-21 levels are high. IL-21 is specifically connected to plaques at skin wounds, too, so blocking IL-21 might be another way to stop new plaques from forming.
Costanzo and his team now are documenting how plaques change when either LL37 or IL-21 is blocked. Recently, their lab research has shown that blocking IL-21 fully prevents the formation of plaques. Eventually, drugs made to stop IL-21, LL37 or both could lower the number of new plaques in patients with psoriasis, especially after minor cuts or scrapes.
Skin cell interactions
Dr. Marinkovich also has conducted research into the immune system and skin cell interactions of psoriasis. As principal investigator at the Stanford University School of Medicine dermatology lab since 1995, Marinkovich studies the roles that genes and cell production play in numerous skin diseases. His Foundation grant project focuses in part on how changes in immune cells lead to psoriatic skin symptoms.
His research evolved from studies of blistering diseases that identified skin cell changes similar to those seen in psoriasis. As a clinician who frequently treats people with psoriasis, Marinkovich was inspired by this research to seek funds for new psoriasis studies. He is testing how changes to inflammatory substances in the skin affect psoriasis plaques.
In psoriasis, inflammatory substances in the immune system and in the skin cause pain, redness and plaque growth. Often, the disease process is studied along with immune cells and many inflammatory substances together. Marinkovich is studying individual inflammatory factors in skin cells that worsen psoriasis to identify the connection between single substances and disease symptoms.
Identifying how individual substances affect plaques can lead to new drugs that block only these substances. Eventually, targeting specific inflammation substances in the skin could lead to new drugs with fewer side effects than current treatments that block the body’s entire immune response, he hopes.
Marinkovich’s research isolates factors important in plaque development to identify their distinct connections to the progression of psoriasis.
When his Foundation grant ends next year, Marinkovich will continue his research with existing funds from the National Institutes of Health (NIH). His ultimate goal is to identify targets for new drugs along the immuneinflammation path.
As researchers continue to identify the multiple ways inflammation and immune-system problems contribute to the development of psoriasis, treatment options will expand and become more specific. The new treatments will target particular molecules and pathways of the disease, not simply minimize symptoms after they occur. National Psoriasis Foundation, through its Translational Grant program and other dedicated support, is playing an integral role in these goals and discoveries.
Nicole Van Hoey is a freelance medical writer based in Arlington, Va.