Treating autosomal dominant polycystic kidney disease by using inhalable thyroid hormone-nanocarriers

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic, rare disease, that causes uncontrolled growth of cysts in the kidney. Slowly, the kidneys lose their ability to filter waste from the blood, which leads progressively to loss of function and kidney failure. There is no cure for ADPKD. Our studies showed that treatment with L-thyroxine (T4) – a hormone that is naturally produced by the thyroid gland and usually reduced in patients with kidney disease – can drastically prevent the progression of the disease. Since T4 regulates several biological processes in our body, it could possibly cause some undesired effects. To strengthen the beneficial effects of T4 and avoid possible undesired ones, here we will develop a nanomedicine-based approach (NanoT4) that can specifically target and deliver T4 to polycystic kidneys. To this end, we will assess the specificity of different NanoT4 systems and their potential to inhibit cyst formation and growth in 3D human models of ADPKD by using microscopy and molecular biology techniques. To guarantee maximum specificity and safety we will fine-tune the doses and timing in vivo through monitoring the levels of NanoT4 in the blood and urine and evaluate its effect in various organs. We will then develop a patient-friendly method for administering NanoT4 systems through the lungs, and finally evaluate their efficacy in preventing cyst growth and disease progression in ADPKD animals. This project aspires to develop a safe and efficient approach for treating ADPKD and to yield important new knowledge about the pathobiology of ADPKD.