Anemia of Inflammation Program

Hemojuvelin & hepcidin antagonists as novel treatments for anemia of inflammation

Anemia of Inflammation (AI) is a commonly acquired disorder that is associated with a variety of conditions including kidney disease, malignancy and other clinical settings of chronic inflammation. Currently available EPO-based therapies have dose-limiting side effects.

To define novel therapeutic targets for the treatment of AI we studied the inherited disorder Juvenile Hemochromatosis (JH) as AI and JH represent opposite ends of the iron phenotypic spectrum. AI is characterized by iron-rich macrophages and impaired intestinal iron absorption which results in restricted iron availability for normal red blood cell production and anemia, whereas in JH, the macrophages are iron-depleted and intestinal iron absorption is enhanced, resulting in total body iron overload.  Loss-of-function mutations in hemojuvelin and hepcidin were found to cause JH and as such, antagonists of either or both of these targets should reverse the iron disturbances in AI and treat the disorder in a new and more physiological manner.

We have a strategic partnership with Isis Pharmaceuticals to develop antisense therapeutics targeting hemojuvelin and hepcidin. As these targets are expressed in the liver and have been largely inaccessible using traditional drug discovery methods, they are ideally suited to antisense therapeutics. XEN701 is the first antisense drug that targets the hepcidin-hemojuvelin pathway to enter development from our collaboration with Isis Pharmaceuticals. Antisense drugs targeting hemojuvelin and hepcidin should provide therapeutic benefit to patients with AI by reversing iron disturbances and thereby facilitating red blood cell production.