Project ID: TECH2026-01

Background

Polycystic Kidney Disease (PKD) affects 1 in 500 people. Half of PKD of patients reach kidney failure by age 50. Annual U.S. healthcare costs exceed $120 billion. There is currently no cure and a few affective treatments.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the progressive development of renal cysts, which ultimately leads to end-stage renal disease (ESRD). ADPKD affects over 600,000 people in the United States and over 12 million people worldwide, with no cure currently available. The hallmark of the disease is abnormal tubular cell proliferation and fluid secretion leading to progressive enlargement of cysts and kidney failure. Current therapies, like vasopressin V2 receptor antagonists, shown only modest delay of disease progression and often lead to sever side effects, including hepatotoxicity and polyuria. The drug, Tolvaptan, slows disease progression but has major drawbacks, such as: hepatotoxicity risk, high cost, and limited ability to prevent cyst growth or kidney decline.

There is a compelling need for therapies that target cellular mechanisms driving cyst formation and disease progression. There is a need for safer therapeutic treatments that address the mechanistic root of the disease with fewer side effects.

Description

Researchers at the University of Toledo have developed therapeutic compositions and methods for targeting the muscarinic acetylcholine receptors (MR) signaling pathway to treat, prevent, or ameliorate kidney disease.

Applications

• Treatment for patients with autosomal dominant polycystic kidney disease.

Advantages

• Approach centers on MR activation to restore impaired intracellular calcium ([Ca⁺2]i) homeostasis and regulate abnormal cell proliferation, two key contributors to cyst formation and disease progression.
• This approach is distinct from previous strategies that target cAMP production or general signaling cascades, offering a more specific treatment that modulates the cilia-associated pathway and addresses underlying dysfunction.
• The use of MR as a dual therapeutic target for both cyst reduction and blood pressure control in ADPKD patients adds significant clinical value.
• Approach introduces a therapeutic mechanism by targeting M3R, a receptor not previously associated with ADPKD treatments.

IP Status:                   Patent Pending

Keywords:      Polycystic, kidney disease, treatment, muscarinic, acetylcholine, receptors