Systems Pharmacology & Disease Control
‘Systems pharmacology’ denotes the application of systems biology approaches to research questions arising in pharmacology. The aim is to understand the interaction of drugs with infectious agents, cells, tissues and entire organisms and to use this knowledge to develop- and improve medical therapy.
While therapeutics aim to reduce disease burden, they can be evenly valuable for epidemiologic control of infectious diseases. However, drug treatment and prophylaxis against infectious diseases always bears a risk for drug resistance development. While resistance can emerge in the individual, transmitted drug resistance may affect the dynamics of an entire disease epidemic. It is thus of utmost importance to understand the systems pharmacology of therapeutics in order to suggest useful schemes for disease control using them, and to prevent resistance emergence and -spread.
In this research group, we address key unsolved mathematical challenges arising in systems pharmacology and develop stochastic models with a particular focus on HIV and Influenza. For example, we assess how different drug combinations and -application schemes affect disease dynamics in individual patients. Furthermore, we aim to assess and to computationally explore the evolutionary space in which HIV can develop drug resistance, with the aim of steering this adaptation process into ‘evolutionary lobster-traps’ using medical treatment as external controls. Consequently, we develop novel optimal control frameworks and numerical methods for their solution. These methods can be applied to control disease dynamics at the epidemic level, as well as optimal treatment of the individual patient.
Max von Kleist
M. von Kleist, S. Winkelmann and Ch. Schütte. Accepted in Comm. Math. Sci. (2013); Markov Control Processes with Rare State Observation: Theory and Application to Treatment Scheduling in HIV-1
M. von Kleist, P. Metzner, R. Marquet and Ch. Schütte. PLoS Comput. Biol.8, e1002359 (2012); HIV-1 Polymerase inhibition by nucleoside analogs: Cellular- and kinetic parameters of efficacy, susceptibility and resistance selection.
M. Frank*, M. von Kleist*, A. Kunz, G. Harms, Ch. Schütte and C. Kloft. Antimicrob. Agents Chemother 55, 5529, (2011) Quantifying the impact of nevirapine-based prophylaxis strategies to prevent mother-to-child transmission of HIV-1: A combined pharmacokinetic, pharmaco- and viral dynamic analysis to predict clinical outcomes.