Spatial evaluation of long-term metabolic changes induced by cisplatin nephrotoxicity.

Cisplatin is a widely used chemotherapeutic agent. However, it is causing nephrotoxic side effects including a reduced glomerular filtration rate and acute kidney injury. Although kidneys can recover to an extent from the treatment, long-term damage is possible.

Targeted inhibition of activated protein C by a non-active-site inhibitory antibody to treat hemophilia.

Activated protein C (APC) is a plasma serine protease with antithrombotic and cytoprotective functions. Based on the hypothesis that specific inhibition of APC's anticoagulant but not its cytoprotective activity can be beneficial for hemophilia therapy, 2 types of inhibitory monoclonal antibodies (mAbs) are tested: A type I active-site binding mAb and a type II mAb binding to an exosite on APC (required for anticoagulant activity) as shown by X-ray crystallography. Both mAbs increase thrombin generation and promote plasma clotting.

Nonclinical Safety Assessment of a Long-Acting Recombinant PEGylated Factor Eight (BAY 94-9027) With a 60 kDa PEG.

BAY 94-9027 (Jivi) is a site-specifically PEGylated human B-domain-deleted (BDD) recombinant factor VIII (FVIII), with a 60 kDa branched PEG molecule attached. The nonclinical safety of BAY 94-9027 was evaluated in a toxicology program that included 2 weeks intravenous (IV) toxicity studies in rats and rabbits, a juvenile toxicity study in rats as well as a 26-week chronic study in rats. Doses of 75, 750, or 2250 IU/kg given every other day for 2 weeks did not elicit any findings related to BAY 94-9027.

Comparison of the MesoScale Discovery and Luminex multiplex platforms for measurement of urinary biomarkers in a cisplatin rat kidney injury model.

Introduction: In the past years several new urinary nephrotoxicity biomarkers have been qualified for use in preclinical studies by the FDA and EMA. Subsequently, kits have been developed to measure these urinary biomarkers on multiplex platforms such as the electro-chemiluminescent based immunoassay from MesoScale Discovery (MSD) and the bead-based immunoassay using Luminex xMAP technology (LMX). The aim of the present study was to compare the two multiplex platforms with respect to the capability of their qualified urinary biomarker panels to measure an increase of these biomarkers relative to histopathological changes in an animal model of nephrotoxicity.