NPA Model Organism Development & Drug Screen

In collaboration with Perlara PBC, Wylder Nation developed NPA fly and worm animal models for NPA using CRISPR gene editing technology.  

In phase one of this project the two main objectives were to generate new small animal disease models, and to discover and validate phenotypes amenable to any kind of high-throughput screen (“screenotypes”), starting with but not limited to drug repurposing and drug discovery screens.  Results of this phase summarized below. (insert poster)

We also characterized NPA patient fibroblasts and optimized this human cell assay to complement the worm model organism assay for a high throughput screening.  

In phase two of this project we screened a 2,560-compound Microsource Spectrum repurposing library on the validated NPA nematode and NPA human fibroblast cell line we developed in phase one.  We identified several compounds that rescue both nematodes and fibroblasts as well as hits that independently rescue each.  

Moving forward we plan to further validate the top 2-3 hits from both screens in the ASMKO mouse model, a widely accepted and validated animal model for NPA.  Wylder Nation holds exclusive rights to all data and any IP generated from this project