Automated High-throughput Behavioral Measurement in Co-Housed Mice for Safer and More Effective Psychiatric Drug Development

Descripción del proyecto

Seguimiento de ratones para el desarrollo de fármacos psiquiátricos

El desarrollo de fármacos para trastornos psiquiátricos y neurológicos requiere de ensayos preclínicos exhaustivos. Sin embargo, los modelos murinos empleados en la actualidad pueden ser costosos y poco fiables. Dado el aumento de la importancia de efectuar evaluaciones éticas en fármacos para el sistema nervioso central, sobre todo a raíz de la epidemia de opiáceos, resulta esencial contar con un sistema automatizado capaz de analizar varios sujetos a la vez, mejorando así la eficiencia y la precisión. En el proyecto HOMECAGE, financiado por el Consejo Europeo de Investigación, se desarrollará una plataforma para el seguimiento continuo de múltiples sujetos en sus entornos sociales naturales. Este sistema cumplirá con las normas de la industria y se centrará en la evaluación del riesgo de adicción y la preferencia por la sacarosa, dos pruebas básicas relacionadas con la depresión y la ansiedad. Permitirá la observación precisa de ratones cohabitados, lo cual servirá como un «microscopio del comportamiento» para mejorar el análisis de la conducta en roedores.

Objetivo

Drug development for psychiatric and neurological disorders requires extensive preclinical testing for validation of safety and efficacy. Preclinical investigation of Central Nervous System (CNS) - acting drugs is primarily performed using traditional lab assays in rodent models. These experiments are typically based on manual analysis of isolated subjects, requiring huge investment in lab animals and technicians for brief measurements. These preclinical experiments are consequently subject to multiple sources of noise, and experience failures in prediction of clinical efficacy and safety. The need therefore exists for a scalable and automated preclinical experimental system for continuous parallel analysis of multiple co-housed subjects.

To address this industry need, we will develop the HOMECAGE—a first-of-its-kind, automated platform for continuous and parallel monitoring of the performance of multiple subjects in their native social environment. We will adapt HOMECAGE to industry standards, including its expansion to a broad range of preclinical experimental paradigms, and perform a comprehensive investigation of the IP landscape and appropriate business strategies for commercialization.

Increased vigilance in assaying the abuse liability of CNS-acting drugs has erupted following the opioid crisis, exemplifying the industry need for efficient, effective and ethical methodologies for preclinical assessment. Addiction liability and sucrose preference, most relevant to depression and anxiety, are the primary preclinical assays on which project HOMECAGE will focus.

The breakthrough automated system provided by HOMECAGE will facilitate continuous and accurate simultaneous monitoring of co-housed mice, acting as a revolutionary ‘behavioral microscope’ for radically improved throughput and increased resolution in the preclinical analysis of rodent behavior.