FEB 13, 2019 10:30 AM PST

Accurate Clinical Concentration-Response Predictions for Cardiac Arrhythmias Using a Population-Based in Vitro/In Silico Model

Speaker
  • Professor, Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University
    BIOGRAPHY

Abstract

Xenobiotic-induced cardiotoxicity is a major concern for both pharmaceuticals and chemicals in the marketplace. For drugs, "Thorough QT/corrected QT (QTc)" (TQT) studies are cornerstones of clinical cardiovascular safety assessment. However, TQT studies are resource intensive, and preclinical models predictive of the threshold of regulatory concern are lacking. For other chemicals, cardiotoxicity is not routinely assessed, and is largely inferred from epidemiologic data.  We hypothesized that an in vitro model using induced pluripotent stem cell (iPSC)-derived cardiomyocytes from a diverse sample of human subjects can serve as a "TQT study in a dish," improving cardiotoxicity assessments for both pharmaceutically and chemicals in commerce. For 10 positive and 3 negative control drugs, in vitro concentration-QTc, computed using a population Bayesian model, accurately predicted known in vivo concentration-QTc. Moreover, predictions of the percent confidence that the regulatory threshold of 10 ms QTc prolongation would be breached were also consistent with in vivo evidence. This "TQT study in a dish," consisting of a population-based iPSC-derived cardiomyocyte model and Bayesian concentration-QTc modeling, has several advantages over existing in vitro platforms, including higher throughput, lower cost, and the ability to accurately predict the in vivo concentration range below the threshold of regulatory concern.  These results demonstrate the potential for replacing a multi-million dollar clinical trial – the Thorough QT/QTc study – with an in vitro-in silico model.  Moreover, because cardiotoxicity clinical trials are not performed for non-pharmaceuticals, such a model could fill a critical gap in chemical toxicity testing.  

Learning Objectives: 

1. Describe current practices in cardiotoxicity assessment for xenobiotics.
2. Explain how induced pluripotent stem cell-derived cardiomyocytes may be useful in advancing cardiotoxicity assessment.


Show Resources
You May Also Like
MAY 11, 2021 10:00 AM PDT
C.E. CREDITS
MAY 11, 2021 10:00 AM PDT
Date: May 11, 2021 Time: 10:00zm PDT Your samples are some of the most valuable assets in the laboratory. After spending countless hours on extraction and preparation, your conclusions could...
SEP 14, 2021 7:00 AM PDT
C.E. CREDITS
SEP 14, 2021 7:00 AM PDT
Date: September 14, 2021 Time: 7am PDT, 10am EDT, 4pm CEST A conventional thermal cycler has long been a commodity product in the lab and end-point PCR techniques can be completed almost wit...
JUN 09, 2021 7:00 AM PDT
C.E. CREDITS
JUN 09, 2021 7:00 AM PDT
Date: June 9, 2021 Time: 09 June 2021, 7am PDT, 10am EDT, 4pm CEST cells with dramatic implications on the validity of past cell culture related research. The fact that at least 509 cell lin...
SEP 29, 2021 11:00 AM PDT
C.E. CREDITS
SEP 29, 2021 11:00 AM PDT
Date: Septembr 29, 2021 Time: 11:00am (PDT), 2:00pm (EDT) 3D cell models are becoming increasingly popular for studying complex biological effects, tissue functionality, and diseases. While...
JUL 15, 2021 8:00 AM PDT
C.E. CREDITS
JUL 15, 2021 8:00 AM PDT
Date: July 15, 2021 Time: 8:00am (PDT), 11:00am (EDT) High dimensional full spectrum flow cytometry grants unprecedented access to previously unattainable parameters in cellular biology. Flu...
OCT 14, 2021 9:00 AM PDT
C.E. CREDITS
OCT 14, 2021 9:00 AM PDT
Date: October 14, 2021 Time: 9:00am (PDT), 12:00pm (EDT), 5:00pm GMT Western blot analysis is a method widely used in the lab today because of its versatility in detecting and measuring spe...
FEB 13, 2019 10:30 AM PST

Accurate Clinical Concentration-Response Predictions for Cardiac Arrhythmias Using a Population-Based in Vitro/In Silico Model


Specialty

Animal Research

Animal Models

Life Science

Cancer Research

Research

Animal Sciences

Immunology

Cell

Cell Biology

Animal Behavior

Neuroscience

Research And Development

Lab Animals

Animals

Clinical Research

Geography

Europe93%

North America3%

Asia2%

Africa2%

Registration Source

Website Visitors100%

Job Title

Student22%

Research Scientist20%

Medical Laboratory Technician13%

Medical Doctor/Specialist13%

Post Doc11%

Scientist9%

Educator/Faculty4%

Clinical Laboratory Scientist2%

Executive2%

Facility/Department Manager2%

Lab Management2%

Organization

Academic Institution57%

Hospital16%

Research Institute9%

Ambulatory Care3%

Industrial Company3%

Pharmaceutical Company3%

Medical Center2%

Government/public2%

Clinical Laboratory2%

Medical School2%

Government2%


Show Resources
Loading Comments...
Show Resources