Treatment of fibrosis-associated pathologies through downstream TGF-β pathway inhibition

Value Proposition

• Inhibits downstream signaling pathway of TGF-β signaling, reducing pleiotropic and off-target effects.
• Selectively targets tissue specific calpains, increasing efficacy as compared to current TGF-β signaling pathway inhibitory methods.
• Applicable to several disease models with specific focus on epithelial-to-mesenchymal transition pathologies.
• Simple development of small molecule therapy through rational drug design or drug screening.

Technology Description

Researchers at Johns Hopkins have identified a novel therapeutic target to inhibit the progression of epithelial-to- mesenchymal transition (EMT) and fibroblast-to-myofibroblast transition (FMT) by specifically targeting tissue-specific calpains that are downstream in the TGF-β signaling pathway. This technology is relevant to fibrosis-associated diseases and cancer, which both can exhibit varying levels of EMT and FMT.

Unmet Need

Current methods for inhibiting the TGF-β pathway to reduce fibrosis target upstream factors, including TGF-β itself. While these methods demonstrate some efficacy, they fail to fully inhibit EMT and FMT. Further, these targets are often pleiotropic, and inhibition can result in deleterious effects. Therefore, there is a strong need for a tissue-specific therapy to inhibit EMT and FMT with high efficacy, without off-target or harmful side effects.

Stage of Development

·       Proof of concept studies have been performed.

·       Patent granted.

Data Availability: Data available upon request.

Publications

1. Kim et al. Calpain 9 as a therapeutic target in TGFβ-induced mesenchymal transition and fibrosis. Science Translational Medicine (2019).