Iron Overload Program

DMT1  inhibitors to treat iron overload disorders.

Iron overload disorders such as hereditary hemochromatosis (HH), and thalassemia intermedia (TI) are characterized by an up-regulation of DMT1 in the intestine and hyper absorption of dietary iron. The hyperabsorption leads to a relatively rapid iron overloading of tissues and toxicities causing significant morbidities such as cardiomyopathy, diabetes, cirrhosis and liver cancer. Thalassemias are the most prevalent genetic conditions worldwide, and of these thalassemia intermedia (TI), is the most common clinical presentation.  It is very common in Asia, Africa and the Mediterranean basin where the number of patients is of the order of many millions.  Hereditary Hemochromatosis (HH) on the other hand, is the most common genetic disorder among individuals of European descent. HH is found at a heterozygous carrier frequency of approximately 1 in 10 and a homozygous frequency of about 1 in 200 and these patients are genetically programmed to hyperabsorb dietary iron.

Genetic studies showed that loss of DMT1 activity causes a severe iron deficiency anemia due to the inability to absorb dietary iron, and as such is opposite of the iron hyperabsorption underlying hereditary hemochromatosis and thalassemia intermedia. Inhibitors of DMT1 activity are therefore predicted to treat the underlying iron hyperabsorptive pathophysiology of these iron overload disorders.

Our DMT1 inhibitor program is in the phase of development candidate selection.