|SS1|| Expanding Concept of Chaperone Therapy for Inherited Brain Diseases
Chaperone therapy is a new concept of molecular therapeutic approach, first developed for lysosomal diseases, utilizing small molecular competitive inhibitors of lysosomal enzymes. This concept has been gradually targeted to many diseases of other categories, utilizing various compounds not necessarily competitive inhibitors but also non-competitive inhibitors or endogenous protein chaperones (heat-shock proteins).
In this session we will discuss current trends of chaperone therapy targeting various types of neurological and non-neurological diseases caused by misfolded mutant proteins. This molecular approach will open a new therapeutic view for wide variety of diseases, genetic and non-genetic, and neurological and non-neurological, in the near future.
Yoshiyuki Suzuki, M.D., Ph.D., Tokyo Metropolitan Institute of Medical Science (Japan).
|SS2|| Quantitative and Systems Pharmacology: Thinking in a wider "systems-level" context accelerates drug discovery and enlightens our understanding of drug action
"Quantitative and Systems Pharmacology (QSP) is an emerging discipline focused on identifying and validating drug targets, understanding existing therapeutics and discovering new ones. The goal of QSP is to understand, in a precise, predictive manner, how drugs modulate cellular networks in space and time and how they impact human pathophysiology." (QSP White Paper - October, 2011)
Over the past three decades, the predominant paradigm in drug discovery was designing selective ligands for a specific target to avoid unwanted side effects. However, in the current post-genomic era, the aim is to design drugs that perturb biological networks rather than individual targets. The challenge is to be able to consider the complexity of physiological responses to treatments at very early stages of the drug development. In this way, current effort has been put into combining 0 chemogenomics with network biology to implement new network-pharmacology approaches to drug discovery; i.e. polypharmacology approaches combined with systems biology information, which advance further in both improving efficacy and predicting unwanted off-target effects. Furthermore, the use of network biology to understand drug action outputs treasured information, i.e for pharmaceutical companies, such as alternative therapeutic indications for approved drugs, associations between proteins and drug side effects, drug-drug interactions, or pathways and gene associations which provide leads for new drug targets that may drive drug development.
Following the line of QSP Workshops I and II (2008, 2010), the QSP White Paper (2011), or QSP Pittsburgh Workshop (2013), the goal of this symposium is to bring together interdisciplinary experts to help advance the understanding of how drugs act, with regard to their beneficial and toxic effects, by sharing new integrative, systems-based computational or experimental approaches/tools/ideas which allow to increase the probability that the newly discovered drugs will prove therapeutically beneficial, together with a reduction in the risk of serious adverse events.
Violeta I. Perez-Nueno, Ph.D., Senior Scientist, Harmonic Pharma, Nancy (France).