Reviewing preclinical models of diabetic heart failure in pursuit of new treatments

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A group of top drug researchers has published a high-impact review that provides guidance on how preclinical studies of diabetes heart failure should be designed in a way that is most similar to the human condition.

The Monash Institute of Pharmaceutical Sciences led the review published in Trends of Pharmacological Sciences. The review examined the preclinical models currently available for investigating diabetes-induced heart disease (also known as DC). It highlighted their strengths, weaknesses, and identified new translational opportunities that could be used to address the unmet medical need of DC.

Professor Rebecca Ritchie, MIPS Drug Discovery Biology Theme Lead, stated that preclinical models are a crucial component in understanding the causes of disease and is essential for the discovery new targeted treatments.

“Diabetic patients are more likely to develop cardiac abnormalities that increase susceptibility and heart failure. However, there is no cure for DC and a clinical need that remains urgent.

“We hope that, by providing fellow researchers with a comprehensive understanding about the pros and cons of current preclinical DC models it will help address knowledge gaps and pave way for possible new treatments.”

The main difference between the two types is that type I diabetes is a genetic disorder and often appears early in life. Type II is largely diet-related and develops over time. Therefore, preclinical models of DC must be tailored to the characteristics of each type.

Dr. Darnel Prakoso, who is the Monash Heart Failure Pharmacology Team’s first author, said: “In the present review we dissected pre-clinical models type-1 and type-2 diabetic models of cardiomyopathy and how they can mimic the cardiac pathology found in human DC.”

Researchers emphasize that there is no preclinical model that accurately mimics the observational characteristics of diabetes-induced cardiomyopathy. Therefore, it is important to consider the purpose of the study when choosing a model.

“For example, if the study is to study the progression of type-1 diabetic-induced cardiomyopathy, a preclinical model that produces a spontaneous immune response, mimicking what is seen at the clinic, is likely to be the best. Dr. Prakoso said that a model that is well-characterized and does not contain genetic manipulation is recommended for cases where specific pathways or proteins are being dissected.

“There is still much to learn about the specific mechanisms that cause DC. Preclinical models are a key component of the drug discovery pipeline. Professor Ritchie stated that the closer we get to modeling human disease in these models, we will be able to develop new treatments to those with DC.

Uncontrolled diabetes can lead to heart failure, from the early stages to the late stages.

More information:
Darnel Prkoso et. al. Current landscape of preclinical diabetic cardiomyopathy models. Trends in Pharmacological Science (2022). DOI: 10.1016/j.tips.2022.04.005

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Monash University

Preclinical models for diabetic heart failure: A review (2022, July 5)
Retrieved 5 July 2022
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