Quantitative Systems Pharmacology in Neuroscience: Novel Methodologies and Technologies

Peter Bloomingdale, Tatiana Karelina, Murat Cirit, Sarah F. Muldoon, Justin Baker, William J. McCarty, Hugo Geerts, Sreeraj Macha
2021 CPT: Pharmacometrics & Systems Pharmacology  
The development and application of quantitative systems pharmacology models in neuroscience have been modest relative to other fields, such as oncology and immunology, which may reflect the complexity of the brain. Technological and methodological advancements have enhanced the quantitative understanding of brain physiology and pathophysiology and the effects of pharmacological interventions. To maximize the knowledge gained from these novel data types, pharmacometrics modelers may need to
more » ... d their toolbox to include additional mathematical and statistical frameworks. A session was held at the 10th annual American Conference on Pharmacometrics (ACoP10) to highlight several recent advancements in quantitative and systems neuroscience. In this mini-review, we provide a brief overview of technological and methodological advancements in the neuroscience therapeutic area that were discussed during the session and how these can be leveraged with quantitative systems pharmacology modeling to enhance our understanding of neurological diseases. Microphysiological systems using human IPSC cells, digital biomarkers, and large-scale imaging offer more clinically relevant experimental datasets, enhanced granularity, and a plethora of data to potentially improve the preclinical-to-clinical translation of therapeutics. Network neuroscience methodologies combined with quantitative systems models of neurodegenerative disease could help bridge the gap between cellular and molecular alterations and clinical endpoints through the integration of information on neural connectomics. Additional topics, such as the neuroimmune system, microbiome, single-cell transcriptomic technologies and digital device biomarkers, are discussed in brief.
doi:10.1002/psp4.12607 pmid:33719204 pmcid:PMC8129713 fatcat:whbfagi6k5bs7cnv2w76fd7wf4