Project Leader:   
Paul Goldberg

Lead Institution:   
Xenon Pharmaceuticals

Technology Applications:   
Iron overload treatment, genetic disease treatment

Research Funding Program:   
Translational Program for Applied Health

Iron is essential to bind oxygen and transport electrons for all living organisms, but excess iron levels are toxic and can cause diabetes, liver cirrhosis, heart disease and arthritis. Over 100,000 Canadians have a genetic disease called Hereditary Hemochromatosis (HH) that results in toxic accumulation of iron.

The only current treatment is blood-letting, or phlebotomy, which is a highly invasive and uncomfortable treatment option for those suffering with HH. Similarly, conditions including anemias and thalassemias are treated with blood transfusions that can also lead to increased iron levels in the body. A safe and effective oral therapeutic would be an excellent alternative or adjuvant treatment for those affected by iron accumulation disorders. The project lead by Xenon Pharmaceuticals and Dr. Paul Goldberg will determine a suitable candidate for clinical trials through testing a set of candidate drugs that prevent iron absorption in the intestine.

DMT1 is the major iron transporter in the intestine and inhibition of this early step in the absorption pathway will provide a treatment for HH. A group of DMT1 inhibitors have been identified and are currently being tested for efficacy so that a single candidate can be identified to enter clinical trials. Phase one clinical trials will involve giving healthy volunteers single ascending doses of the inhibitor to generate Proof of Concept results and to assess any potential side effects. This project will identify DMT1 inhibitors suitable for entry into Phase one clinical trials where initial safety and early proof of concept will be defined.

Another group of patients that suffer from iron overload are people that require blood transfusions because of diseases such as anemias and thalassemias. Transfusion patients are treated with iron chelators to control iron excess but this treatment can have severe side effects and is not fully effective. The underlying anemia also stimulates intestinal iron absorption exacerbating the accumulation of iron in the body; therefore decreasing iron absorption from the diet by inhibiting DMT1 may provide an adjuvant therapy for transfusion recipients.