FEB 14, 2019 12:00 PM PST

Application of Micro-Physiological Systems for Respiratory Drug Discovery: Opportunities and Challenges

C.E. CREDITS: RACE
Speakers
  • Senior Investigator and Group Leader, Respiratory Biology, Novartis Institutes for BioMedical Research
    Biography
      David J. Rowlands, Ph.D is a Senior Investigator and group leader within the Respiratory Diseases Area at the Novartis Institutes for Biomedical Research (NIBR). Before joining NIBR, David was a postdoctoral research at Columbia University, New York City focused on elucidating novel mechanisms responsible for regulating severity of lung inflammation following injury. Throughout his career, David has utilized a multi-disciplinary approach to address scientific questions with a strong focus on utility of in vivo pharmacology and translational ex vivo and in vitro model systems to replicate physiological process. Over the last 8 years at NIBR, David and his team have enabled and supported multiple drug discovery programs spanning diseases including COPD, cystic fibrosis, pulmonary arterial hypertension and idiopathic pulmonary fibrosis at all stages of the drug discovery pipeline from target validation through to support of a PhII clinical trial. Although in vivo pharmacology remains a key focus of David's group, over the last few years, his team have increasingly incorporated alternative systems to address complex scientific questions including use of ex vivo tissue preparations such as the isolated perfused lung or ex vivo tracheal tissue to a more recent consideration of microfluidic 'organ on a chip' technology.

    Abstract:

    The lung is a highly complex organ, comprised of more than 40 cell types that are responsible for various important functions, the lung’s complexity contributes to the subsequent challenges with developing complex in vitro co-culture models (also called micro-physiological systems or (MPS) or organs-on-ships). In vivo pharmacology naturally fulfills an important role in drug discovery, enabling benchmarking and selection of lead compounds against a particular target and understanding of PK/PD relationships to enable clinical dose prediction and calculation of safety margins amongst other roles.  

    Although there are a myriad of considerations and limitations in the development and qualification of such in vitro systems, MPS exhibit great promise in the fields of pharmacology and toxicology. Successful development and implementation of MPS may enable assessment of human translation of mechanistic responses observed in non-clinical species, potentially increasing the clinical relevance of efficacy or safety endpoints, while decreasing overall animal use. This article summarizes, from the pharmaceutical industry perspective, essential elements in the development and qualification of lung MPS that MPS developers and manufacturers can adapt to facilitate the rapid implementation of these models for safety evaluation during the drug development process.

    Learning Objectives: 

    1. What role can ex vivo models and ‘lung-on a-chip’ model play in respiratory drug discovery? 
    2. A look into the future: considerations for design and utility of the next generation micro-physiological systems for respiratory drug discovery  


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