Stem cells helped find a potential treatment for psoriasis

In a new study, scientist have discovered biological processes that may explain why the skin thickens with psoriasis. This can help in the development of new treatments for the disease.

To date, there is no effective targeted therapy for the treatment of psoriasis. At least 100 million people worldwide suffer from this skin disease. The skin affected by psoriasis thickens, becomes red and have silvery-white flakes, called scales. Patients may have deformed nails and psoriatic arthritis — inflammation of the joints – may develop.

Scientists have already found out what exactly happens in the body of a patient with psoriasis and how to alleviate his/her condition, but it remains unclear what causes these pathological changes and how they can be prevented.

“Psoriasis places social and psychological stress on patients and is associated with risk of diabetes, cardiovascular disease and more. While steroids and biologics can be prescribed, we don’t have a cure because we haven’t understood the cause”, – said co-senior author of an article, published in Journal of Investigative Dermatology, George Murphy, M.D., professor of pathology at Brigham and Women’s Hospital.

“Our initial finding that skin thickening in psoriasis is due to build-up of dysregulated stem cells and their progeny is exciting because it represents a new way of thinking about an old and significant skin disease.”

To better understand the reason for the dysregulation of skin stem cell behavior, the researchers focused on the epigenome – molecular labels that regulate gene activity, but do not change the primary structure of DNA.

“Without understanding the mechanism underlying a disease, it’s hard to find effective treatments”, –  said co-senior author Christine Lian, M.D. associate professor of pathology at Brigham and Women’s Hospital. “The question we decided to pursue was: Is there an epigenetic abnormality in psoriasis that may explain why stem cells are misbehaving?”

Liane, Murphy, and colleagues found a defect in the DNA epigenome that led to the loss of a specific epigenetic marker, known as 5-hmC. The defect was found in the cells of patients with psoriasis, but not in skin of patients with other diseases that cause a similar thickening of the skin, such as callous-like areas from chronic irritation. The team reproduced the defect in a mouse model of psoriasis and found that it predominantly affects genes that regulate the function of skin cells.

Earlier, Lian and Murphy showed that the loss of 5-hmC in skin epigenome can be reprogrammed using compounds such as, for example, ascorbic acid (vitamin C). They believe that therapeutic correction of an epigenomic defect in psoriasis can reverse the disease process.

Based on experiments using skin stem cell cultures in the laboratory, the team saw promising preliminary results suggesting that 5-hmC levels could be restored to make up for the deficiency seen in psoriasis.

Researchers note that while the role of vitamin C is of great interest, more research is needed to develop and test effective treatments, since simply taking a vitamin supplement would likely have little effect. The team’s next steps include testing other epigenetic reprogramming compounds on three-dimensional models of skin stem cells.

“If successful, our epigenetic stem cell explanation for psoriasis hopefully could transform therapy, allowing for more personalized and targeted approaches directed at the very cells that accumulate to form the heartbreak of this all-too-often devastating skin condition”, – Murphy said.