Alterity Therapeutics (ASX:ATH) has announced that new data on its lead drug candidate, ATH434, was presented at the World Orphan Drug Congress USA 2024 in Boston.
The poster, 'Biophysical Characteristics of ATH434, a Unique Iron-Targeting Drug for Treating Friedreich’s Ataxia', was presented by Ashley Pall, Department of Pharmaceutical Sciences at Wayne State University.
Alterity said the study evaluated the ability of ATH434 to target the toxic form of iron that drives the pathology of Friedreich’s Ataxia, a rare neurodegenerative disease that affects young children and young adults.
The study also evaluated traditional iron chelators designed to bind and remove iron from the body. Conversely, an iron chaperone is designed to bind and redistribute iron within the body.
“This investigation provides important insights into the mechanism of action of ATH434, namely that it selectively targets the labile iron implicated in the pathology of important neurodegenerative diseases. In this way, ATH434 behaves like a chaperone to redistribute iron within the body. There has historically been great interest in targeting iron in general to treat these diseases, and we now have clear evidence that ATH434 is very different from traditional iron chelators,” said Dr David Stamler CEO of Alterity.
The study investigated how strongly ATH434 or traditional iron chelators bind the two forms of cellular iron: ferric iron, the stored form, or ferrous iron, the form required for vital cellular functions such as energy production.
In excess, the ferrous or 'labile' iron can also promote oxidative stress in diseases like Friedreich’s Ataxia, as in Parkinson’s disease and Multiple System Atrophy.
Dr. Stamler continued, “The genetic defect in Friedreich’s Ataxia leads to reduced function of frataxin, a protein necessary for utilizing labile iron, thus leading to iron accumulation in disease. By acting as an iron chaperone, ATH434 has potential to reduce labile iron levels and thus slow disease progression. Given these new data, we are excited to evaluate FA as a potential new indication for ATH434.”
The company said the novel iron binding properties of ATH434 presented in the poster support its characterisation as an iron chaperone based on properties it shares with endogenous iron chaperones such as frataxin and poly-C binding proteins. These include its low micromolar binding affinity for ferrous iron and a bound structure that may allow for the transfer of ferrous iron proteins involved in cellular function.