According to a recent study, epigenetic medications that have shown promise in cancer trials greatly lessen scarring in the cells of people who have the fatal and incurable autoimmune illness scleroderma.
Fibrosis, a development of tissues that resemble scar tissue in the skin and internal organs, is a long-term immune system disorder known as scleroderma. This process takes place when cells that make up connective tissue, known as fibroblasts, create excessive amounts of collagen, hardening the patient’s skin and organs and causing tissue damage and organ failure.
In a recent study, scientists from Michigan Medicine concentrated on BETs, which are proteins that control the expression of genes by binding to changes on the proteins around which DNA is wrapped. This process is known as epigenetic regulation.
Several pharmaceutical firms have created BETs-targeting medications, particularly one isoform known as BRD4. According to research published in JCI Insight, BRD4 inhibitors, which are known to contribute to cancer, also have an impact on scleroderma fibrosis.
BRD4 inhibitors were tested on the skin fibroblasts of scleroderma patients as well as in mouse skin fibrosis models. They discovered that the therapy reduced scarring in both animal and human-derived cell lines.
Through this study, we have uncovered a new class of epigenetic drugs that can be used in scleroderma fibrosis. If we can repurpose these drugs and get them through development more quickly, we can provide faster relief for patients who struggle with debilitating symptoms of this autoimmune disease. The process can typically take around 10 years, but our patients cannot wait that long.
Pen-Suen Tsou (Eliza)
In preclinical investigations, the inhibitors utilized by researchers at Michigan Medicine have demonstrated promise in the treatment of several malignancies. In particular, AZD5153, a medication utilized in the recent study, is being evaluated in a Phase I clinical trial for lymphomas and sarcomas.
“Through this study, we have uncovered a new class of epigenetic drugs that can be used in scleroderma fibrosis,” said Pen-Suen Tsou (Eliza), Ph.D., senior author of the paper and a rheumatology researcher at Michigan Medicine.
“If we can repurpose these drugs and get them through development more quickly, we can provide faster relief for patients who struggle with debilitating symptoms of this autoimmune disease. The process can typically take around 10 years, but our patients cannot wait that long.”
The Scleroderma Program at Michigan Medicine collaborated on the investigation. Additionally, Tsou’s team discovered a previously unknown effect of the calcium signaling protein CaMKII on fibrosis in scleroderma.
“Right now, we are doing some follow up studies to see if inhibitors of this protein can block scarring for scleroderma,” Tsou said. “This opens up a brand-new direction for us to offer a novel target for this disease.”
Additional authors include: Sirapa Vichaikul, B.S., Mikel Gurrea-Rubio, Ph.D., M. Asif Amin, M.D., Phillip L. Campbell, B.S., Qi Wu, Ph.D., Megan N. Mattichak, William D. Brodie, Pamela J. Palisoc, B.S., Mustafa Ali, B.S., Sei Muraoka, M.D., Ph.D., Jeffrey H. Ruth, Ph.D., Ellen N. Model, B.S., Dallas M. Rohraff, B.S., M.P.H., Jonatan L. Hervoso, B.S., Yang Mao-Draayer, M.D., Ph.D., David A. Fox, M.D., Dinesh Khanna, M.B.B.S., M.Sc., all of Michigan Medicine, and Amr H. Sawalha, M.D., University of Pittsburgh.
