From Animal Models to Clinical Practicality: Lessons Learned from Current Translational Progress in Diabetic Peripheral Neuropathy Research

Diabetic peripheral neuropathy (DPN) is a leading risk factor for diabetes‐related mortality and morbidity. Despite promising effects in animal models, none of the pharmacological agents has been successfully translated into effective treatments in humans. Challenges faced by investigators seeking to translate results from animal models into human trials include marked species differences in genotype and behavior, nerve structure and metabolism, duration of diabetes, and tissue vulnerability. While animal experiments have provided much of our understanding of the disease biology, these species differences necessitate a careful reevaluation of the validity of data obtained from experimental approaches. Therefore, we examined these pathogenetic treatments and summarized their clinical outcomes in treating DPN. Moreover, we examined the most commonly used rodent models during preclinical drug screening, including STZ‐diabetic rats and db/db mice. By putting previous observations generated by animal studies into perspective, we investigated the salient features and predictability of these models in relation to the pathophysiological and pharmacological outcomes in diabetic patients. In particular, we identified the molecular, cellular and physiological differences that significantly impair the translation from experimental approached to human clinical setting. We conclude that these findings should be taken into critical consideration by researchers as limitations for efficient pharmacological translation.