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Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges.

Publication ,  Journal Article
Geerts, H; Wikswo, J; van der Graaf, PH; Bai, JPF; Gaiteri, C; Bennett, D; Swalley, SE; Schuck, E; Kaddurah-Daouk, R; Tsaioun, K; Pelleymounter, M
Published in: CPT Pharmacometrics Syst Pharmacol
January 2020

The substantial progress made in the basic sciences of the brain has yet to be adequately translated to successful clinical therapeutics to treat central nervous system (CNS) diseases. Possible explanations include the lack of quantitative and validated biomarkers, the subjective nature of many clinical endpoints, and complex pharmacokinetic/pharmacodynamic relationships, but also the possibility that highly selective drugs in the CNS do not reflect the complex interactions of different brain circuits. Although computational systems pharmacology modeling designed to capture essential components of complex biological systems has been increasingly accepted in pharmaceutical research and development for oncology, inflammation, and metabolic disorders, the uptake in the CNS field has been very modest. In this article, a cross-disciplinary group with representatives from academia, pharma, regulatory, and funding agencies make the case that the identification and exploitation of CNS therapeutic targets for drug discovery and development can benefit greatly from a system and network approach that can span the gap between molecular pathways and the neuronal circuits that ultimately regulate brain activity and behavior. The National Institute of Neurological Disorders and Stroke (NINDS), in collaboration with the National Institute on Aging (NIA), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), and National Center for Advancing Translational Sciences (NCATS), convened a workshop to explore and evaluate the potential of a quantitative systems pharmacology (QSP) approach to CNS drug discovery and development. The objective of the workshop was to identify the challenges and opportunities of QSP as an approach to accelerate drug discovery and development in the field of CNS disorders. In particular, the workshop examined the potential for computational neuroscience to perform QSP-based interrogation of the mechanism of action for CNS diseases, along with a more accurate and comprehensive method for evaluating drug effects and optimizing the design of clinical trials. Following up on an earlier white paper on the use of QSP in general disease mechanism of action and drug discovery, this report focuses on new applications, opportunities, and the accompanying limitations of QSP as an approach to drug development in the CNS therapeutic area based on the discussions in the workshop with various stakeholders.

Duke Scholars

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Published In

CPT Pharmacometrics Syst Pharmacol

DOI

EISSN

2163-8306

Publication Date

January 2020

Volume

9

Issue

1

Start / End Page

5 / 20

Location

United States

Related Subject Headings

  • Systems Biology
  • Pharmacology
  • Humans
  • Drug Discovery
  • Drug Development
  • Central Nervous System Diseases
  • Central Nervous System Agents
  • Animals
  • 3214 Pharmacology and pharmaceutical sciences
  • 3208 Medical physiology
 

Citation

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Geerts, H., Wikswo, J., van der Graaf, P. H., Bai, J. P. F., Gaiteri, C., Bennett, D., … Pelleymounter, M. (2020). Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges. CPT Pharmacometrics Syst Pharmacol, 9(1), 5–20. https://doi.org/10.1002/psp4.12478
Geerts, Hugo, John Wikswo, Piet H. van der Graaf, Jane P. F. Bai, Chris Gaiteri, David Bennett, Susanne E. Swalley, et al. “Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges.CPT Pharmacometrics Syst Pharmacol 9, no. 1 (January 2020): 5–20. https://doi.org/10.1002/psp4.12478.
Geerts H, Wikswo J, van der Graaf PH, Bai JPF, Gaiteri C, Bennett D, et al. Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges. CPT Pharmacometrics Syst Pharmacol. 2020 Jan;9(1):5–20.
Geerts, Hugo, et al. “Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges.CPT Pharmacometrics Syst Pharmacol, vol. 9, no. 1, Jan. 2020, pp. 5–20. Pubmed, doi:10.1002/psp4.12478.
Geerts H, Wikswo J, van der Graaf PH, Bai JPF, Gaiteri C, Bennett D, Swalley SE, Schuck E, Kaddurah-Daouk R, Tsaioun K, Pelleymounter M. Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges. CPT Pharmacometrics Syst Pharmacol. 2020 Jan;9(1):5–20.
Journal cover image

Published In

CPT Pharmacometrics Syst Pharmacol

DOI

EISSN

2163-8306

Publication Date

January 2020

Volume

9

Issue

1

Start / End Page

5 / 20

Location

United States

Related Subject Headings

  • Systems Biology
  • Pharmacology
  • Humans
  • Drug Discovery
  • Drug Development
  • Central Nervous System Diseases
  • Central Nervous System Agents
  • Animals
  • 3214 Pharmacology and pharmaceutical sciences
  • 3208 Medical physiology