The Science

Current therapies for Parkinsonian disorders treat the symptoms and NOT the underlying pathology of the disease. At Alterity, we are focused on “changing the state” of people living with neurodegenerative diseases, from disease → health. We do this by targeting the underlying pathology to potentially develop a disease modifying therapy.

The approach with our lead asset, ATH434, can be summarized with three key concepts, or THE THREE R’s: Redistribute, Reduce, and Rescue.

REDISTRIBUTE: We know there is excess, loosely bound iron in the brains of patients with MSA. And it is known that this increased iron contributes to the pathology of the disease. ATH434 is able to bind this excess iron and REDISTRIBUTE it within the body. Importantly, ATH434 does not deplete the body’s iron, which we need for normal physiology like generating energy or allowing many enzymes to function. Instead, ATH434 removes it from areas where it is causing damage and puts it back into circulation or safe storage.

REDUCE: It is well known that excess loosely bound iron has an adverse impact in the brains of patients with MSA and Parkinson’s disease, as it contributes to the misfolding and aggregation of an important brain protein called α‑synuclein.

Excess iron is also the root cause of oxidative stress, a process which generates free radicals that damage intracellular lipids and organelles such as DNA and mitochondria, neuroinflammation and cellular toxicity. By redistributing excess loosely bound iron, ATH434 REDUCES α-synuclein aggregation and oxidative stress.

RESCUE: By REDISTRIBUTING the excess iron and REDUCING α-synuclein aggregation and oxidative stress, ATH434 can RESCUE neurons in multiple regions of the brain, protecting them from future damage. By limiting neurodegeneration, we are addressing the underlying pathology of the disease and potentially changing the course of illness.

ATH434 has successfully completed Phase 1 studies which demonstrate it is rapidly absorbed, has a half-life that supports twice-daily dosing and was well tolerated. At clinical doses, ATH434 achieves brain concentrations that exceed efficacious levels in animal models of disease. ATH434 is currently being studied in a randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage MSA.

Alterity is continually seeking to innovate and discover novel drug candidates that will improve the lives of individuals with neurological diseases. Our patentable and innovative new chemical scaffolds leverage structure-activity relationship insights that have been developed over years of testing and validation by Alterity scientists. In addition, we are continually expanding our translational research activities through rich academic collaborations.

We continue to search for additional uses for our clinical candidates in a diverse array of diseases.