Please join us on Thursday, October 18th for the 2012 AAPS PPDM Open Forum,
McCormick Place, Chicago: Systems Therapeutics: Attaining Intimate
Understanding by Unraveling Complexity.
Register for this open forum at http://www.aaps.org/AMRegister/
Objectives:
1. To provide an overview of quantitative systems pharmacology approaches
2. To identify and discuss key issues regarding methodology and utility of QSP
3. To identify and discuss major barriers to implementing this holistic approach
The majority of drugs are developed to combat disease by focusing on a single
intercession point (single-pathway targeted approaches). However, often the
results achieved are suboptimal and therapeutic failures are not realized until
the conduct of clinical proof of concept (POC) studies. Arguably, the largest
hurdle to improving POC outcomes is the quantitative bridging of target
modulation to clinical manifestations. Such links would fill the void of
incomplete understanding and provide early, model-informed support of
therapeutic targets. Quantitative links would bring meaning to the
multiplicity and complexity of genetic and epigenetic changes during disease,
and elucidate redundancies and cross-talk found in key signaling pathways.
Thus, quantitative systems pharmacology (QSP) approaches aimed at understanding
the global physiologic environment of the targets and the whole-body effects of
modulation by therapeutic candidates would improve the probability of drug
development success. QSP models provide an approach to quantitatively analyze
biological and physiological complexity and generate understanding of how
multi-scale biological systems function, by viewing the organism as an
integrated, and interacting, network of genes, proteins, biochemical reactions,
and endocrine feedbacks. Instead of analyzing individual components or aspects
of the organism, QSP models aim to holistically examine all the components and
the interactions among them, to understand the orchestrated outcome of the
entire system in response to disease and therapeutic intervention.
By integrating across disciplines and available quantitative approaches (e.g.,
systems biology, genetic modeling, agent-based, PK/PD), QSP can provide
mechanistic understanding of a target, potential therapeutic, the potential
adverse effects, and knowledge gaps. Models may include components for
increasing understanding of how a drug acts in various tissues and cell types,
as well as potential issues arising from multiple actions within a single cell
type due to the presence of several interacting pathways. Thus, QSP models can
be important translationally to help identify new drug targets, predict adverse
events and improve the safety and efficacy of existing drugs prior to entering
humans. This implied goal of identifying high probability candidates early is
especially important in complex diseases such as cancers, psychiatric disorders
and metabolic syndrome. Through QSP paradigm and actual applied models
presentations attendees will receive an introduction to the developing field of
QSP modeling and obtain an appreciation for how these concepts and models are
being applied to drug discovery and development. Discussion will center on
issues regarding methodology, utility, effectiveness, and barriers to
implementation.
Topics and speakers:
1. "Why do applied mathematics and systems biology matter and do these
approaches yield valuable targets for drug development?" Speaker: Dr. Piet van
der Graaf, Department of Pharmacometrics, Global Clinical Pharmacology, Pfizer
2. "Do models of organ-level physiology and target drug action aid the
understanding or design of drug induced organ injury?" Speaker: Dr. Amin
Rostami, Professor of Systems Pharmacology, University of Manchester
3. "Is it feasible to attempt a more holistic understanding of drug effects by
consideration of coherence of multipathway networks of signaling, metabolism,
and gene expression?" Speaker: Dr. Matt Riggs, Principal Scientist II/Group
Leader, Systems Biology M&S, Metrum Research Group LLC
4. "Can the collaboration between pharmacologists, clinicians, and systems
biologists be promoted/enhanced?" Speaker: Dr. Mark Peterson, Director
Pharmacometrics, Global Clinical Pharmacology, Pfizer
For more information:
http://www.aaps.org/Meetings_and_Professional_Development/Conference_Mini_Sites/2012_AAPS_Annual_Meeting_and_Exposition/content/Open_Forum%E2%80%94Systems_Therapeutics__Attaining_Intimate_Understanding_by_Unraveling_Complexity/
Steering Committee:
Douglas H. Sweet, Chair - Virginia Commonwealth University, USA
Jenny Chien - Eli Lilly and Company, USA
Liesbeth de Lange - LACDR/Pharmacology, NL
Bernd Meibohm, University of Tennessee Health Sciences Center
Di Wu (Chair Systems Biology FG) - The Children's Hospital of
Philadelphia/University of Pennsylvania