SPC5001 / Roche - LARVOL DELTA

Predicting nucleic acid drug-induced nephrotoxicity using a 3D human renal proximal tubule spheroid model. (PubMed, J Toxicol Sci) - "Significant ATP depletion was observed only after prolonged exposure to SPC5001, a nephrotoxic antisense oligonucleotide. In contrast, biomarker expression and HCA facilitated early detection of compound-specific toxicity and implicated endoplasmic reticulum and mitochondrial stress as underlying mechanisms. These findings establish 3D-RPTEC as a sensitive and physiologically relevant platform for predicting the nephrotoxic potential of nucleic acid drugs."

Biomarker • Journal • Hematological Disorders • Thrombocytopenia • KIM1

Nephrotoxic antisense oligonucleotide SPC5001 induces kidney injury biomarkers in a proximal tubule-on-a-chip. (PubMed, Arch Toxicol) - "Moreover, perfusate levels of biomarkers KIM-1, NGAL, clusterin, osteopontin and VEGF increased 2.5 ± 0.2-fold, 3.9 ± 0.9-fold, 2.3 ± 0.6-fold, 3.9 ± 1.7-fold and 1.9 ± 0.4-fold respectively, in response to SPC5001, generating distinct time-dependent profiles. In conclusion, target downregulation, cytotoxicity and kidney injury biomarkers were induced by the clinically nephrotoxic ASO SPC5001, demonstrating the translational potential of this kidney on-a-chip."

Biomarker • Journal • Acute Kidney Injury • Nephrology • Renal Disease • CLU • KIM1 • MALAT1 • SPP1