Dr. Richard Sontheimer discusses a new class of small molecule oral drugs to treat later stage disease of systemic sclerosis.
Richard D. Sontheimer, MD, is a clinical professor of dermatology at the University of Utah School of Medicine.
“This patient creates a lot of angst when they show up in our clinics because it’s one of the most frustrating, hardest to treat, and most ravaging kind of diseases on individuals that we see in dermatology,” says Richard D. Sontheimer, MD.
In his presentation, “What’s New in the Autoimmune Connective Tissue Diseases,” at Maui Derm 2021, Dr. Sontheimer emphasizes the complexities of scleroderma pathology. It’s understood to be the result of a genetically dysregulated immune response with certain environmental triggers that produces immune-mediated microvascular damage.
“And these events coming together characteristically in autoimmune scleroderma to produce a lot of fibrosis. And that’s what causes the namesake scleroderma: hard skin.”
Dr. Sontheimer’s focus here, specifically, is the fibrotic stage.
“Is there anything we can do to to slow down fibrosis, to reverse fibrosis?”
UVA1 photo therapy has some anti-fibrotic and anti inflammatory effect, he says. There are monoclonal antibodies to the TGF-beta receptor, which is involved in the pro fibrosis pathway. Those are being studied now in systemic sclerosis.
There is also a new class of small molecule oral drugs that seems to have both an anti-inflammatory and anti-fibrotic effect. The first of its kind in this series, pirfenidone is a small molecule that was FDA-approved in 2014 for idiopathic pulmonary fibrosis that may help to decrease fibrosis by blocking the TGF-beta receptor and the PDGF receptors, and may also have an immunomodulating effect.
Dr. Somtheimer cites a review1 that examines other types of small oral molecule potential drugs that may clinically impact the fibrosis pathway and possibly provide some hope and some benefit to treating the later stage disease of systemic sclerosis.
Reference
- Tsou PS, Haak AJ, Khanna D, Neubig RR. Cellular mechanisms of tissue fibrosis. 8. Current and future drug targets in fibrosis: focus on Rho GTPase-regulated gene transcription. Am J Physiol Cell Physiol. 2014 Jul 1;307(1):C2-13. doi: 10.1152/ajpcell.00060.2014. Epub 2014 Apr 16.
