The therapeutic target for the PRS-080 molecule and the EUROCALIN Consortium is a disease pattern termed anemia of chronic disease (ACD). This is a condition marked by a deficiency of red blood cells or of hemoglobin in the blood, resulting in pallor and weariness. Under certain conditions (such as chronic infection, chronic immune activation, or malignancy) iron - which carries oxygen in red blood cells - is reduced in the body.

The major pathophysiological factor in ACD is retention of iron, rendering the metal ion unavailable for generation of red blood cells (erythropoiesis). Anemia in patients with chronic kidney disease (CKD) – a serious indication affecting approximately 4.5 million European patients - is often treated by administering erythropoiesis-stimulating agents (ESA) such as EPO.

Many patients with CKD and anemia can be effectively treated with ESA‘s. However, around 10 % of patients (~ 150,000 patients in the EU) are hypo- or non-responsive to ESA, leaving them without an effective treatment option. The important role of ESA resistance has been demonstrated by the results of clinical trials that reported an increased mortality or morbidity in patients who received high doses of ESA but did not reach the targeted hemoglobin plasma concentration. Increased mortality rates in anemic cancer patients treated with high ESA doses have recently been observed, raising yet additional safety concerns. In addition, the urgent need for new therapies to combat ACD is reflected by the fact that a large fraction (about 40-50 %) of anemic cancer patients are hypo or unresponsive to ESA therapy (~740,000 patients in the EU). Therefore, the development of alternative treatment strategies for ACD, specifically in patients with chronic kidney disease and cancer, is of utmost importance.

The exact mechanism of ACD is not fully understood but current results strongly suggest that a small protein, a peptide named hepcidin plays a very important role in regulating the iron balance in the body. Hepcidin is synthesized in the liver, enters the blood stream and binds tightly to the iron channel protein ferroprotein, which is found amongst others on the surface of reticulendothela cells. These cells store iron. If hepcidin therefore binds to ferroprotein it prevents the secretion of iron, thereby functionally reducing iron absorption. As a consequence, the body cannot effectively use iron to make new red blood cells and the number of healthy new red blood cells gradually falls.

The Consortiums goal is to tackle ACD by binding hepcidin to the PRS-080 Anticalin. Anticalin-bound hepcidin is unable to block ferroprotein and iron can be put back into the blood system.
For more information about the disease, please refer to:

The Iron Disorders Institute: http://www.irondisorders.org/anemia-of-chronic-disease
The International BioIron Society: http://bioiron.org/
The Wikipedia entry of ACD.
More information on Anticalins can be found here.