Targeted Epigenetic Therapy against Distal Regulatory Element of TGFB2 Expression for Scleroderma and Fibrotic Disease

Unmet Need
Scleroderma disorders comprise a heterogeneous group of conditions linked by the presence of thickened, sclerotic skin lesions. These conditions result in a poor quality of life and have a poor prognostic outcome. In particular, systemic sclerosis (SSc) has a 10 year mortality rate of approximately 30%. However, the pathogenic mechanisms of SSc remain unclear and clinical management is limited to non-specific and largely non-efficacious therapy. Consequently, novel disease-modifying therapeutics are needed to improve outcomes for patients with SSc and other fibrotic disorders.

Technology Overview
JHU researchers have demonstrated that patient-derived SSc fibroblasts overexpress a cytokine, TGFβ2, which results in elevated expression of fibrillar collagen, and ultimately fibrosis. Through targeted epigenetic editing, they discovered an epigenetic enhancer that is critical in the upregulation of TGFβ2 expression in patients with diffuse systemic sclerosis. The inventors have identified pharmaceutical approaches that are capable of targeting this distal regulatory element to normalize TGFβ2 expression and treat Scleroderma-induced fibrosis. Importantly, this approach may also be useful in the prevention or treatment of other fibrotic and TGFβ2-mediated diseases.

Stage of Development
JHU researchers have demonstrated that certain pharmacological compositions are disease-modifying for SSc in vitro.

Publications
Shin, JY et al. Epigenetic activation and memory at a TGFB2 enhancer in systemic sclerosis. Sci Transl Med. 2019 Jun 19; 11(497).


 

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