Hematology

Targeting RGMc/HJV

Many diseases and rare genetic mutations can cause disruptions in the body’s ability to maintain stable iron levels, which is also called iron homeostasis. This can cause patients to experience iron deficiency (anemia) or iron overload, which can result in oxidative stress leading to organ damage.

Anemia is associated with many chronic inflammatory diseases, such as chronic kidney disease (CKD). In addition, patients suffering from metabolic disorders, such as diabetes and NASH, are also more susceptible to developing anemia.

Bone morphogenetic proteins (BMPs) are a member of the TGFβ superfamily that regulates a wide range of biological processes, including iron homeostasis in the liver. Within the liver, signaling by BMPs controls the expression of the master regulator of systemic iron homeostasis, hepcidin. This BMP pathway requires a co-receptor named RGMc, or hemojuvelin (HJV), which has a specific role in iron homeostasis compared to the broader role of BMPs in the body. By targeting RGMc/HJV directly rather than BMPs, such as BMP6, we can achieve exquisite selectivity for modulation of iron homeostasis, without impacting other important cellular processes controlled by BMPs.