Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET.

Polycystic kidney disease (PKD) is characterized by the development of fluid-filled kidney cysts and relentless progression to renal failure. Current treatments have adverse effects and limited efficacy, enhancing the need for improved therapeutics. Here, we provide a proof of concept for the use of dimeric immunoglobulin A (IgA) (dIgA) monoclonal antibodies (mAbs) to target epithelial-enclosed cysts, by exploiting their ability to transcytose via the polymeric immunoglobulin receptor highly expressed on renal cyst-lining cells.

Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a widespread genetic disease that leads to renal failure in the majority of patients. The very first pharmacological treatment, tolvaptan, received Food and Drug Administration approval in 2018 after previous approval in Europe and other countries. However, tolvaptan is moderately effective and may negatively impact a patient's quality of life due to potentially significant side effects.