We at Inotiv are thrilled to receive a $1.8 million dollar grant from the Peer Reviewed Medical Research Program from the U.S. Department of Defense (DOD) to develop a novel chronic kidney disease (CKD) in vivo model that can bridge the gap between current translational models and human renal research. Translational models of CKD are important tools in understanding complex disease pathways and how potential therapeutics can mitigate or even cure kidney disease.

According to the Centers for Disease Control and Prevention (CDC), more than 1 in 7 US adults have some degree of CKD, with approximately 35.5 million Americans affected by the disease. Focal and segmental glomerulosclerosis (FSGS) is the most common disease affecting the glomeruli (filtration units of the kidney), causing progressive scarring, leading to nephrotic syndrome, which is characterized by massive amounts of proteins present in the urine. Apolipoprotein L1 (APOL1) is a component of the innate immune system, and the discovery of APOL1 high-risk variants (G1 and G2) in 2010 helped the scientific community understand why some individuals are at higher risk for CKD.

Inotiv’s researchers intend to develop and characterize two genetically engineered mouse lines using the latest technologies including CRISPR-Cas9. The first humanized APOL1 mouse line is expected to express APOL1 systemically (full body), closely mimicking the human expression of APOL1. The second humanized mouse line is expected to express APOL1 exclusively in the kidneys. Together, these transgenic mouse lines are anticipated to fully represent the human APOL1-associated nephropathy as a complex system and uncover the impact of the specific APOL1 G2 high risk variant on renal function, the kinetics of kidney disease onset, and the progression to FSGS and renal failure.

“We’re keenly aware of the significant gap in the chronic kidney disease research area when it comes to translational in vivo models for CKD,” said Flavia Gomes Machado, leading the project at Inotiv. “The development and phenotypic characterization of this novel APOL1 model can help facilitate bridging that gap and lead to a better understanding of CKD and the therapeutics that mitigate a disease that plagues so many individuals.”

Scott Daniels, Inotiv’s Senior Vice President, Discovery and Translational Sciences, concluded, “Inotiv is committed to supporting medical research and innovation, and has assembled a world-class team of discovery scientists to accelerate our customers’ translational research programs. The award of this grant demonstrates our success, and the confidence of our customers in our ability to help them tackle the most complex biological and therapeutic challenges in pursuit of bringing much needed new medicines to patients.”

Learn more about Inotiv’s Renal Pharmacology Program.