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Apr 1, 2009 (Vol. 29, No. 7)

Getting a Handle on Metabolic Disorders

Targets and Methods Vary, but the End-Goal Is the Same—More Effective Therapeutics

  • Animal Models

    Alain Stricker-Krongrad, Ph.D., senior scientific advisor at Charles River Laboratories, works with client researchers to plan and develop animal models that are scientifically valid for their disease state of interest. Dr. Stricker-Krongrad employs the use of animal models that provide his clients with an assessment of the efficacy and drug safety of the drugs they’re developing. The rodent models used include rats and mice that have been bred to display cardiovascular and or diabetic indications consistent with these disease states. 

    “Our process is to monitor different biomarkers of metabolic disease while keeping an eye on cardiovascular involvement,” Dr. Stricker-Krongrad said. “In the development of drug therapeutics for obesity, the challenge continues to be the ability to monitor the impact of the therapeutic intervention. Specifically, our work is focused on the development of a meaningful animal model that will enable researchers to screen drug impacts and determine outcomes earlier in the development process. The term coined for this approach, translational medicine, is a broad term that I don’t like to use because it detracts from the real question: How predictive is the animal model for the human condition?”

    At the meeting, Dr. Stricker-Krongrad introduced a new animal model now available at Charles River while focusing on the current tools available to calculate cardiovascular risk. In drug development, the observation is that off-target effects of a drug given to normal patients don’t always reveal themselves. Unless the target patient population is tested you can’t determine the off-target impact of the drug candidate. 

    That is, it is likely that the obese patient with diabetic or cardiac issues may show an adverse off-target effect not otherwise observed. The key is to identify or develop a good animal model to monitor the level of risk early in the development process.  All drugs have a toxicity risk to some level, Dr. Stricker-Krongrad said, the key is to identify just how severe that risk is. Among the biomarkers of choice for this risk assessment are the troponins, and these markers can serve to differentiate risk populations.

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