The RAGE Inhibitor TTP488 (Azeliragon) Improves Diabetic Bladder Dysfunction in Leptin-Deficient Obese Mice

Area of Science:

• Urology
• Endocrinology
• Pharmacology

Background:

• The advanced glycation end product (AGE)-RAGE axis is linked to diabetic bladder dysfunction (DBD).
• The therapeutic potential of RAGE blockade in DBD remains unexplored.

Purpose of the Study:

• To investigate the effects of the RAGE inhibitor TTP488 (azeliragon) on functional and molecular aspects of diabetic bladder dysfunction in leptin-deficient (ob/ob) mice.

Main Methods:

• Administration of TTP488 to ob/ob mice and wild-type controls.
• Assessment of bladder AGEs, RAGE levels, antioxidant enzyme activities, collagen intensity, voiding parameters, and ex vivo bladder contractility.

Main Results:

• TTP488 treatment reduced AGEs and collagen in ob/ob mouse bladders, normalizing antioxidant enzyme activities.
• TTP488 improved bladder voiding function and contractility without affecting body weight or glucose metabolism.
• No changes in RAGE levels were observed in bladder tissues after TTP488 treatment.

Conclusions:

• RAGE blockade with TTP488 effectively mitigates diabetic bladder dysfunction in a mouse model.
• RAGE inhibition presents a promising therapeutic strategy for managing diabetic bladder dysfunction.