Can We Develop Translational Platforms that Model Multiple Aspects of Human Diabetes?
A significant challenge in the development of new anti-diabetic therapies is the lack of translational platforms that can model the pre-diabetic state, diabetes progression, and all the other components of human metabolic syndrome, disease pathophysiology, and associated diabetic comorbidities. Recently a new study(1) from the Tufts Center for the Study of Drug Development showed that compared to other drugs, developing anti-diabetic drugs is riskier, from a clinical translation perspective. The likelihood that a diabetes drug entering clinical testing would transition to Phase III testing was 12.8%, vs. 21.1% for all drugs(1). This underscores the importance of having translational animal models of diabetes that can enable development and approval of anti-diabetic drugs.
Why is it so Challenging?
Some of the most commonly used rodent models do not recapitulate the multiple components of human diabetes, or they rely on monogenic mutations not represented in the human population. These existing models usually mimic specific components of human disease, which in turn limits their translatability.
Why is Translatability of Animal Models so Important?
Anti-diabetic therapies in development are often aimed to address multiple aspects of the disease. However, many drug development programs employ the use of multiple animal models, each mimicking some aspect of the disease. This creates a challenge as it requires validation and adoption of multiple animal models and one bases key go/no-go decisions in the context of “stitching together” data from multiple animal models that are not translational to the human condition. Using animal models that mimic specific and narrow aspects of the disease to understand efficacy and PK/PD of the drug hinders the development of a translational solution.
So What is the Solution?
Over the last few decades of running diabetes studies with conventional models such as the ZDF rat, ob/ob mice, db/db mice, DIO mice and rats, at CrownBio, we listened to our customers’ frustrations regarding the lack of translatability of these conventional models. We embarked upon a program to systematically address this issue. We worked with industry partners to develop and validate rodent and non-human primate (NHP) models of diabetes(2,3). Summarized in the table below our platforms:
- are highly translatable and progressively develops many human-like features of diabetes and metabolic syndrome while on a normal chow diet, allowing evaluation of pharmacological intervention at different disease stages
- have an intact leptin pathway like human diabetic patients
- provide a translatable platform to model diabetic complications, such as nephropathy, neuropathy, and osteoporosis.
CrownBio’s cardiovascular and metabolic disease portfolio brings to the research community an entire platform of translational models (e.g. the ZDSD Rat, the FATZO Mouse, and NHP Models) to help overcome the translatability challenge as we strive to help the research community eradicate this debilitating disease.
- Tufts CSDD Impact Report Single Issue, Impact Report Vol. 18 No.05
- Characterization of the ZDSD Rat: A translational model for the study of metabolic syndrome and type 2 diabetes. Peterson RG, Jackson CV, Zimmerman K, de Winter W, Huebert N, Hansen MK. J Diabetes Res. 2015;2015:487816. doi: 10.1155/2015/487816. Epub 2015 Apr 16. PMID: 25961053 (Collaborative study with Janssen Pharmaceutical)
- Pioglitazone Increases Whole Body Insulin Sensitivity in Obese, Insulin-Resistant Rhesus Monkeys. Tozzo E, Bhat G, Cheon K, Camacho RC. PLOS ONE. 2015; 10(5): e0126