Unmet Need: Prevalence of Type 2 Diabetes (T2D) continues to rapidly increase worldwide, contributing significant economic and global health burdens. There is an urgent need for the development of novel therapeutic strategies to treat T2D.
Technical Details: Johns Hopkins researchers have identified a novel target to treat T2D and report here the development of a method to screen for unique T2D therapeutics that modulate the target, zinc transporter ZnT8. Inhibition of ZnT8 as a T2D treatment strategy is supported by the finding that gain-of-function mutations in ZnT8 increase the risk of developing T2D while loss-of-function mutations serve a protective role. Therefore, investigators have designed an in vitro assay to screen for novel therapeutic compounds by quantifying ZnT8 utilizing highly specific monoclonal antibodies generated against ZnT8. Using the developed screening assay, it was shown that exposure of human insulinoma cells to pro-inflammatory cytokine treatment in vitro results in a detectable decrease in ZnT8 expression in cells. Overall, identification of ZnT8 modulators will provide first-in-class compounds targeting a novel mechanism for treatment of T2D and can be applied to other diseases.
Value Proposition:
• Novel method to identify ZnT8 modulators
• Simple assay design conducive to high-throughput candidate screening
• Identified hits can be used in the treatment of Type 2 Diabetes, Type 1 Diabetes and other diseases
Looking for Partners to: Develop & commercialize the technology as a screening assay to identify novel ZnT8 modulators to treat disease.
Stage of Development: Pre-Clinical
Data Availability: In vitro
Inventors: Dax Fu and Chengfeng Merriman
Patent Status: PCT Pending: 17/108,441
Publication(s): Merriman, C and Fu, D. (2019). Down-regulation of the islet-specific zinc transporter-8 (ZnT8) protects human insulinoma cells against inflammatory stress. J Biol Chem 294(45):16992-17006.
Gu, Y et al. (2020). Novel autoantibodies to the β-cell surface epitopes of ZnT8 in patients progressing to type-1 diabetes.
