NU 2022-202

INVENTORS

Pinelopi Kapitsinou*

Ratnakar Tiwari

SHORT DESCRIPTION

Inhibition of MCT4 slows the progression of acute kidney inury to chronic kidney disease

BACKGROUND

Acute kidney inury (AKI) is a sudden onset of kidney dysfunction, often caused by factors such as ischemia, toxins, or infections, leading to impaired filtration and accumulation of waste products in the blood. If not adequately managed, AKI can progress to chronic kidney disease (CKD) and contribute to long-term kidney damage. A critical complication of AKI is fibrosis, a process where excessive connective tissue develops in the kidneys, leading to scarring and permanent damage; this fibrosis can hinder the kidney’s ability to repair itself. Novel therapeutic strategies are needed to prevent the transition from AKI to CKD.

ABSTRACT

Northwestern researchers have developed a therapy for AKI which targets the monocarboxylate transporter 4 (MCT4), a lactate transporter upregulated under hypoxic conditions. Researchers induce ischemic acute kidney injury in wild type mice and administer the MCT4 inhibitor syrosingopine. Following treatment with the MCT4 inhibitor, kidneys in the treated group are visually better perfused, demonstrate a 62% reduction in fibrosis histologically, and show significant reduction in levels of prefibrotic inflammatory genes. Taken together, these results indicate a potential novel therapeutic for AKI that can be successfully administered following injury, preventing the transition to chronic kidney disease.

APPLICATIONS

• Treatment for acute kidney injury/fibrosis

ADVANTAGES

• Inhibits long-term disease progression to chronic kidney disease

• Various targeting mechanisms including inhibiting, suppressing, or genetic targeting

IP STATUS

US patent application filed

Kidneys treated with MCT4 inhibitor have increased levels of blood perfusion and decreased levels of fibrotic tissue.