Computational neurosciences and quantitative systems pharmacology: a powerful combination for supporting drug development in neurodegenerative diseases

AbstractSuccessful clinical development of new therapeutic interventions is notoriously difficult, especially in neurodegenerative diseases, where predictive biomarkers are scarce and functional improvement is often based on patient ’s perception, captured by structured interviews. As a consequence, mechanistic modeling of the processes relevant to therapeutic interventions in CNS disorders has been lagging behind other disease indications, probably because of the perceived complexity of the brain. However in this report, we develop the argument that a combination of Computational Neurosciences and Quantitative Systems Pharmacology (QSP) modeling of molecular pathways is a powerful simulation tool to enhance the probability of successful drug development for neurodegenerative diseases. Computational Neurosciences aims t o predict action potential dynamics and neuronal circuit activation that are ultimately linked to behavioral changes and clinically relevant functional outcomes. These processes can not only be affected by the disease state, but also by common genotype variants on neurotransmitter-related proteins a nd the psycho-active medications often prescribed in these patient populations. Quantitative Systems Pharmacology (QSP) modeling of molecular pathways allows to simulate key pathological drivers of dementia, such as protein aggregation and neuroinflammatory responses. They often impact neurotransmit ter homeostasis and voltage-gated ion-channels or lead to mitoch...
Source: Journal of Pharmacokinetics and Pharmacodynamics - Category: Drugs & Pharmacology Source Type: research