Related Experiment Video
Updated: Feb 15, 2026
Absolute Quantification of Plasma MicroRNA Levels in Cynomolgus Monkeys, Using Quantitative Real-time Reverse Transcription PCR
Published on: February 12, 2018
Sustained plasma hepcidin suppression and iron elevation by Anticalin-derived hepcidin antagonist in cynomolgus
Andreas M Hohlbaum1, Hendrik Gille1, Stefan Trentmann1
1Pieris Pharmaceuticals, GmbH, Freising, Germany.
Background And Purpose:
Anaemia of chronic disease (ACD) has been linked to iron-restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25 amino acid hepatocyte-derived peptide that controls systemic iron homeostasis. Here, we report the engineering of the human lipocalin-derived, small protein-based anticalin PRS-080 hepcidin antagonist with high affinity and selectivity.
Experimental Approach:
Anticalin- and hepcidin-specific pharmacokinetic (PK)/pharmacodynamic modelling (PD) was used to design and select the suitable drug candidate based on t1/2 extension and duration of hepcidin suppression. The development of a novel free hepcidin assay enabled accurate analysis of bioactive hepcidin suppression and elucidation of the observed plasma iron levels after PRS-080-PEG30 administration in vivo.
Key Results:
PRS-080 had a hepcidin-binding affinity of 0.07 nM and, after coupling to 30 kD PEG (PRS-080-PEG30), a t1/2 of 43 h in cynomolgus monkeys. Dose-dependent iron mobilization and hepcidin suppression were observed after a single i.v. dose of PRS-080-PEG30 in cynomolgus monkeys. Importantly, in these animals, suppression of free hepcidin and subsequent plasma iron elevation were sustained during repeated s.c. dosing. After repeated dosing and followed by a treatment-free interval, all iron parameters returned to pre-dose values.
Conclusions And Implications:
In conclusion, we developed a dose-dependent and safe approach for the direct suppression of hepcidin, resulting in prolonged iron mobilization to alleviate iron-restricted erythropoiesis that can address the root cause of ACD. PRS-080-PEG30 is currently in early clinical development.
Related Concept Videos
01:43Sustainable Development
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
03:12Freezing Point Depression and Boiling Point Elevation
The boiling point of a liquid is the temperature at which its vapor pressure is equal to ambient atmospheric pressure. Since the vapor pressure of a solution is lowered due to the presence of nonvolatile solutes, it stands to reason that the solution’s boiling point will subsequently be increased. Vapor pressure increases with temperature, and so a solution will require a higher temperature than will pure solvent to achieve any given vapor pressure, including one...
01:26Design Example: Sustainability in Concrete Building
There are multiple approaches to achieve sustainability in a commercial concrete building. For instance, construct a concrete parking area under the building, utilizing pervious concrete paver blocks in open areas to facilitate rainwater collection through an underground...
01:20Elevation of Intermediate Points on Vertical Curves
01:24Cholinergic Antagonists: Pharmacokinetics