RAGE as a Therapeutic Target

Although RAGE antagonism has yet to be tested in clinical trials, preclinical studies using sRAGE, anti-RAGE IgG, or ribozymes directed against RAGE in nephropathy models support the relevance of this axis to the pathogenesis of injury in the diabetic kidney (46,50-51). Importantly, in each of these cases, there was no evidence that blockade of RAGE (using sRAGE, anti-RAGE IgG or in RAGE-null mice) altered levels of glucose, insulin, or lipids in the animals. These studies suggest strongly that RAGE is a downstream effector pathway in hyperglycemic injury, and not the cause of initial perturbation. In this context, it is likely that complementary therapies targeting this axis, as well as other established targets, might exert additive benefit in the kidney. Additional strategies to antagonize RAGE, including small-molecule antagonists and siRNA are also possible means to break the cycle of AGE-RAGE perturbation in the diabetic kidney.

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