Characterization of Oral Gut-Selective vs. Systemic JAK Inhibitors in the Mouse Oxazolone Colitis Model
XTalks Webinar Presentation
|SPEAKER:||Whitney Krey-Epstein, Scientist, in vitro Pharmacology, Theravance Biopharma US, Inc|
Dec 18, 2018
Autoimmune diseases such as ulcerative colitis require chronic treatment that often causes systemic immunosuppression, increasing long term cancer and infection risk. Reducing systemic side effects with localized treatment would greatly benefit patients. This webinar will explore the spatial characterization of oral gut-selective versus systemically available JAK inhibitors in the mouse oxazolone model of ulcerative colitis using the GeoMx™ Digital Spatial Profiler (DSP) from NanoString®.
Preclinical in vivo characterization of localized drug inhibition can be challenging. Traditional analysis of gut-selective JAK inhibitors, utilizing whole tissue homogenization, is not able to resolve cell type-specific inhibition. GeoMx allowed for custom, multiplexed, and highly quantitative spatial sampling of mouse colons. Importantly, the platform’s single-cell masking capabilities mean that infiltrating immune cells in the intestinal mucosa can be sampled independently of non-immune tissue. This enabled the characterization of the spatial heterogeneity of the preclinical mouse model and to discriminate the effects of treatments on distinct cell types. Characterizing models up front can shorten time spent on model development, identify complex effects of target inhibition, and better characterize cell types involved with disease progression. By measuring inhibition in multiple cell types in spatially distinct layers of a mouse colon, the featured speaker will show that an oral gut-selective JAK inhibitor has similar inhibition compared to a systemic drug, but with markedly lower systemic exposure.
FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.