Xaviar Michael Jones, MD, on the Potential to Address Unmet Needs in Systemic Sclerosis With RNA Therapeutics

“...Looking at histology findings at the heart level, we were really excited to see that there was less fibrosis, not only [in] the skin, but also in the heart [in the TSK1 mice treated with TY1]… We're still working on [the] mechanism and we have a hint about different cell types as well as different targets, but nevertheless, this is just groundbreaking, and we hope to have something in our hands that can really help patients moving forward to change [not only] their quality of life, but [also] their overall survival.”

Systemic sclerosis is a complex autoimmune condition that causes patients to experience symptoms including fibrosis, vasculopathy, and immune dysregulation. Although the condition varies between patients, it can affect both the skin and the vital organs, including the heart. Currently, there are no disease-modifying treatment options available for systemic sclerosis, and as such great unmet need remains for this patient population.

Xaviar Michael Jones, MD, a postdoctoral research fellow at Cedars Sinai Medical Center, and his colleagues are currently investigating the potential of TY1, a noncoding RNA therapeutic, as a novel treatment for systemic sclerosis. Jones presented promising findings from their preclinical research at the American Heart Association’s (AHA) Scientific Sessions 2023, held November 10-13 in Philadelphia, Pennsylvania.

In an interview with CGTLive™ at the conference, Jones described the current medical understanding of systemic sclerosis and the unmet needs for the population of patients with this disease. He then spoke about the research he presented at the conference, which involved the use of RNA derived from extracellular vesicles. TY1, an RNA strand consisting of 24 nucleotides, was administered to an inflammatory-dependent bleomycin mouse model. Jones noted that they observed a reduction in collagen content and dermal thickness in the treated mice, which received the RNA therapeutic through an oral gavage. He pointed out that the mice also showed decreased lung congestion and lung fibrosis, improvement of the stiffening of the heart, and better performance on exercise assessments. Jones also spoke about further testing with the TSK1 mouse model, which is not inflammatory-dependent.

REFERENCE
1. Jones XM, Ciullo A, Mesquita T, et al. Noncoding RNA drug, TY1, attenuates cardiac fibrosis in two mouse models of systemic sclerosis. Presented at: AHA Scientific Sessions 2023; November 10-13; Philadelphia, Pennsylvania. Mo1068