The biotechnology company Alterity Therapeutics presented data from their lead Friedreich’s ataxia (FA) drug candidate ATH434 at the 2024 US World Orphan Drug Congress.
In FA, a genetic change in the FXN gene coding for the protein frataxin leads to reduced frataxin levels. Frataxin has an important role in using ferrous iron for energy production in cells. This prevents this type of iron from building up to toxic levels. Reduced levels of frataxin in FA mean that ferrous iron can accumulate, damaging cells.
In this study, researchers showed that ATH434 can bind to excess ferrous iron and redistribute it around the body. This prevents the toxic accumulation that leads to cell damage in FA. There are two main types of iron in the body: ferric iron (stored iron) and ferrous iron (for cellular reactions such as energy production). Traditional iron chelation drugs that have been tested as therapies in the past, reduce the levels of both types of iron. This can have a negative effect in cells. These researchers compared traditional iron chelators with ATH434. Their aim was to find out how effectively ATH434 can selectively target excess ferrous iron without targeting ferric (stored) iron.
The researchers saw that ATH434 can remove accumulated ferrous iron. This means it has the potential to slow disease progression in FA. The study showed that ATH434 binds less strongly to stored iron than traditional iron chelation drugs, selectively targeting ferrous iron.
Read the press release on the Alterity Therapeutics website here.
ATH434 has shown positive results in restoring brain iron balance in animal models of Multiple System Atrophy (MSA). TH434 is currently in phase 2 trials for the treatment of early stage and advanced MSA with sites in the UK. Read about this here and here.
