It affects 100,000 persons in the US alone.
Scleroderma, also known as systemic sclerosis, is a group of rare diseases that involve the hardening and tightening of the skin. It may also cause problems in the blood vessels, internal organs and digestive tract. Scleroderma, also known as systemic sclerosis, is one of the rarest autoimmune illnesses that mostly affects women and affects the skin and internal organs.
Dinesh Khanna, M.B.B.S., M.Sc., head of the Michigan Medicine Scleroderma Program, claims that systemic sclerosis, which has the highest mortality rate among rheumatic diseases, is catastrophic. Researchers in rheumatology are continually looking for ways to employ tools and technologies that have been successful in treating other autoimmune and rheumatic diseases because there are currently no licenced medicines for this subset of scleroderma patients.
“We wanted to understand first if there was any clinical benefit of tofacitinib to patients, but we were also asking, what are the differences in the cells of healthy skin versus systemic sclerosis cells…how does the drug work?” said Khanna.
Tofacitinib, an FDA-approved treatment for rheumatoid arthritis, was one option that doctors at Michigan Medicine and the University of Pittsburgh recently investigated for early-stage systemic sclerosis. The study’s objectives included determining the medication’s safety in patients and figuring out how the medication would mechanically function in the disease at the cellular level.
Tofacitinib was well tolerated among patients with early systemic sclerosis, according to a recent study published in JCI Insight. Researchers also observed that the treatment largely affected the protein interferon, which is prevalent in both fibroblasts and keratinocyte cells. 15 individuals with early diffuse cutaneous systemic sclerosis, skin hardness, and organ problems made up the study sample.
In a double-blind, randomised, placebo-controlled experiment, 10 patients received 5 milligrammes of tofacitinib twice day, and the remaining patients received a placebo. No patients who had severe side effects at or prior to the trial’s end were discovered during the 24-week trial period. The modified Rodnan skin score (mRSS) and other assessments were performed with patients to gauge improvement during the course of the trial in order to gauge tofacitinib’s efficacy.
These findings demonstrated that the mean mRSS score and other metrics improved over the course of the study. Additionally, after 24 weeks, patients on placebo switched to open-label tofacitinib, and improvements persisted for the following 24 weeks, demonstrating improvement in the measure.
“We are delighted to find that the drug is safe to use and can be repurposed for systemic sclerosis treatment,” said Khanna, “but what made this study innovatively was the use of single-cell technology.”
Skin samples were taken from research participants at the beginning of the experiment and again six weeks later, whether they had received tofacitinib or a placebo. The mechanism of tofacitinib action in the skin cells of trial participants was then observed by doctors using the relatively recent technology of single-cell RNA sequencing.
“This work highlights the ability of single-cell RNA-sequencing to determine how disease states are maintained and how various cell populations in the skin, both fibroblasts, skin cells, and immune cells communicate, providing unparalleled power to address disease mechanisms, and how drugs, like tofacitinib, work in a disease where they have not previously been used,” said Johann Gudjonsson M.D., Ph.D., professor of dermatology and a collaborator on this study.
Researchers observed that tofacitinib had no effect on T-cells, which are key white blood cells in the immune system. They also learned how the medicine inhibits cells that help produce connective tissue (fibroblasts) and skin cells (keratinocytes).
“Because we found that the drug was working on one part (the mechanism of fibroblasts and keratinocytes), we are now considering if we can combine tofacitinib with another drug with a complementary mechanism in action, to treat early systemic sclerosis without causing toxicity,” explained Khanna.
Researchers must carry out a more thorough investigation and trial to check if their most recent findings are reliable in order to learn more about the medication.
“From this combined effort between Michigan Medicine and the University of Pittsburgh, we know that the drug is safe, and we know that the technology (RNA sequencing) is feasible, now we can start to utilize the technology and find out what type of therapies we can mix and match that will add benefit to patients,” Khanna said.
Parvathy Sukumaran 
