The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. Based on their small size, tissue transparency, and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, will make C. elegans an ideal model system for in vivo drug discovery campaigns.
Description
Investigators at the University of Pittsburgh adapted C. elegans to develop high-throughput and high-content drug screening strategies analogous to cell-based systems. An automated work flow utilizing fluorescence microscopy with integrated image acquisition and data analysis modules was created using transgenic animals expressing fluorescently-tagged proteins. This platform can qualitatively assess different biological processes including growth, tissue development, cell viability, and autophagy. The model system was successfully employed for small molecule screening using transgenic animals with mutant alpha-1-anitrypsin (AT) modeling human liver disease (cirrhosis).
Applications
• High throughput drug screening and disease modeling tool for Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, frontotemporal dementia, and spongiform encephalopathies, among others.
Advantages
• All-liquid work flow that eliminates bottleneck in screening
• Automated image acquisition and data analysis
Invention Readiness
In vivo data
IP Status
https://patents.google.com/patent/US8809617B2; https://patents.google.com/patent/US9844605B2
