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Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
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Drug discovery for diabetic nephropathy: trying the leap from mouse to man
1Lead Generation Biology, Biotechnology Discovery Research, Lilly Research Laboratories, Indianapolis, IN 46285, USA. breyerma@lilly.com
Abstract:
Diabetic nephropathy is the single major cause of kidney failure in the industrialized world and given the emerging global pandemic of diabetes mellitus, its prevalence is expected to only increase. Because of the lack of dynamic biomarkers that define the rate of kidney function loss, there are few proof-of-concept clinical trials for new therapeutics to treat diabetic nephropathy. A molecular understanding of the pathogenesis of diabetic nephropathy also is lacking. These deficiencies are magnified by the fact that most mouse models of diabetic nephropathy fail to show progressive kidney disease. Recently, some mouse models that showed requisite phenotypic changes of diabetic nephropathy have been identified. Validation of results obtained in these experimental models, and showing whether they accurately can predict clinical response to therapeutics in human diabetic nephropathy, must now be established.
Insights
Diabetic nephropathy, a leading cause of kidney failure, lacks dynamic biomarkers and effective mouse models. Further research is needed to validate new models for predicting therapeutic responses in humans.
Area of Science:
- Nephrology
- Diabetology
- Translational Medicine
Background:
- Diabetic nephropathy is a primary driver of kidney failure globally.
- The increasing prevalence of diabetes mellitus exacerbates this issue.
- Current limitations include a lack of dynamic biomarkers and a poor understanding of disease pathogenesis.
Purpose of the Study:
- To address the need for improved preclinical models of diabetic nephropathy.
- To facilitate the development of novel therapeutics for diabetic kidney disease.
- To establish methods for validating experimental models against human clinical outcomes.
Main Methods:
- Identification of novel mouse models exhibiting key diabetic nephropathy phenotypes.
- Characterization of disease progression in these models.
- Planning for validation studies to correlate model outcomes with human clinical trials.
Main Results:
- Recent identification of specific mouse models that display progressive kidney disease characteristic of diabetic nephropathy.
- These models show promise in recapitulating disease phenotypes.
- Further validation is pending.
Conclusions:
- The development of accurate preclinical models is crucial for advancing diabetic nephropathy research.
- Validated models are essential for predicting the efficacy of new treatments in human patients.
- Continued investigation is required to bridge the gap between experimental findings and clinical application.
