Iron overload disease compounds

Problem

Iron overload is problematic in a number of cancers, blood transfusions, diseases, such as sickle cell anaemia, and a lot of medicines used to treat it are toxic and/or unselective (as they remove other essential metals, including calcium, zinc etc.)

If the iron remains in the body it can lead to organ damage through oxidative stress so there is an urgent need to prepare chelators that “wrap around the metal” enabling it to be transported in the blood system and secreted, typically when one urinates. Known iron chelators tend to be toxic with severe side effects.

Overview

Our preliminary data suggests that we have some novel iron chelators with a reduced toxicity profile. We have combined cyclodextrin (CD) with an iron chelating agent called Deferasirox (also referred to as Exjade ©, a registered trademark of Novartis). The drug is fairly toxic alone and we have some data that suggest that the conjugation of the two drugs leads to a lowering of the toxicity.

 

Cover of Chem Med Chem journal

The compound featured on the front cover of ChemMedChem journal.

 

Cyclodextrin is a glucose containing a “doughnut shaped” molecule that has a big cavity which can hold fatty substances, such as cholesterol. CDs are useful in the preparation of cholesterol-free food and in the treatment of Niemann Pick C disease (NPC), which involves the build-up of toxic levels of cholesterol and other fats in cells. The fact that we have a CD-chelator in the same molecule, means we have a dual-action drug against diseases that have lipid and metal (copper) overload. This means we can potentially treat cholesterol/fat build-up and metal overload (both iron and copper) in the treatment of Niemann Pick C.

Potential applications

There are several potential applications:

  • chronic iron overload caused by, for example, beta thalassemia, multiple blood transfusions, Sickle Cell disease and a number of blood cancers termed Myelodysplastic syndromes, or MDS.
  • Niemann Pick C disease, as it also targets copper overload and Wilson's Disease.

IP status

The technology is protected by an International (PCT) patent application WO2019/150138.

Publications


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