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The Science

Our Approach: Develop A Potential Disease Modifying Therapy by Addressing the Key Processes Underlying Neurodegenerative Conditions

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

Our lead candidate, ATH434, is an oral agent which inhibits the aggregation of proteins such as α‑synuclein in the central nervous system of individuals with Parkinson’s disease and related disorders. ATH434 achieves this effect though moderate affinity with the excess loosely bound iron implicated in these diseases, acting as a chaperone to facilitate its removal from inside cells.

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.

Our Continued Search for Superior Disease Modifying Therapeutics

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.

Published Scientific Research

2023
Future of Parkinson’s Disease Conference
Effects of ATH434, a Clinical-Phase Small Molecule with Moderate Affinity for Iron, in Hemiparkinsonian Macaques

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2023
International Symposium on the Autonomic Nervous System (AAS)
Relationship between N-acetylaspartate and neurofilament light chain in multiple system atrophy

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2023
2023 Society for Neuroscience
Potent Antioxidant and Mitochondrial-protectant Effects of ATH434

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2023
2023 International Congress of Parkinson’s Disease and Movement Disorders (MDS)
A Multimodal Approach is Needed to Accurately Diagnose Early Multiple System Atrophy

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2023
2023 International Congress of Parkinson’s Disease and Movement Disorders (MDS)
Preliminary evidence for evolution of myoinositol and N-acetylaspartate as biomarkers of disease severity in early-stage Multiple System Atrophy

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2023
American Academy of Neurology 2023
2022
Neurotherapeutics Journal
Title: ATH434 Rescues Pre-motor Hyposmia in a Mouse Model of Parkinsonism | SpringerLink

ATH434 Rescues Pre-motor Hyposmia in a Mouse Model of Parkinsonism

2022
American Autonomic Society Annual Meeting 2022
2022
American Neurological Association (ANA)
2022
American Academy of Neurology®
Title: Iron Accumulation Correlates with Disease Severity in Patients with Multiple System Atrophy

2022 Annual Meeting | P15 – Poster Session 15 (aan.com)

2022
Journal of Parkinson’s Disease
Title: “The Compound ATH434 Prevents Alpha-Synuclein Toxicity in a Murine Model of Multiple System Atrophy”

The Compound ATH434 Prevents Alpha-Synuclein Toxicity in a Murine Model of Multiple System Atrophy – IOS Press

2021
International Parkinson and Movement Disorder Society Virtual Congress 2021
Title: “Non-invasive imaging markers of iron accumulation in Multiple System Atrophy”

alterity-threapeutics-non-invasive-imaging-markers-of-iron-accumulation-in-msa–mds-2021.pdf (secureserver.net)

2021
Journal of Parkinson’s Disease
Title: “ATH434 Reverses Colorectal Dysfunction in the A53T Mouse Model of Parkinson’s Disease”

https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd212731?resultNumber=0&totalResults=8&start=0&q=ath434&resultsPageSize=10&rows=10 

2021
Movement Disorders - Journal of the International Parkinson and Movement Disorder Society
Study demonstrating that ATH434 reduces α‑synuclein related neurodegeneration in a widely accepted murine model of Multiple System Atrophy (MSA)

http://doi.org/10.1002/mds.28714 

2021
American Neurological Association (ANA)
Title: ATH434 Preserves Dopaminergic Neurons, Reduces α-synuclein Oligomerization, and Improves Motor Function in a Transgenic Murine Multiple System Atrophy Model

ATH434 protects brain cells and improves motor function – Alterity Therapeutics

2021
American Autonomic Society Annual Meeting 2021
Title: Cardiovascular safety and pharmacokinetics of ATH434, a novel small molecule inhibitor of α-synuclein aggregation, in adults and older adults

Alterity Therapeutics Announces Presentation of ATH434 at the American Autonomic Society Virtual Meeting 2021 – Alterity Therapeutics

2020
American Academy of Neurology®
Title: A Phase 1 Study of PBT434, a Novel Small Molecule Inhibitor of α-Synuclein Aggregation, in Adult and Older Adult Volunteers (4871)

https://n.neurology.org/content/94/15_Supplement/4871

2019
American Academy of Neurology®
Title: A First in Human Study of PBT434, a Novel Small Molecule Inhibitor of α-Synuclein Aggregation (S4.001)

https://n.neurology.org/content/92/15_Supplement/S4.001

2019
International Congress of Parkinson’s Disease and Movement Disorders®

2018
International Congress of Parkinson’s Disease and Movement Disorders®
Title: PBT434 prevents the accumulation of glial cell inclusions and insoluble alpha‐synuclein in a mouse model of Multiple System Atrophy.
2017
Acta Neuropathologica Communications Neuroscience of Disease
Title: The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson’s disease. The novel compound PBT434 prevents iron mediated neurodegeneration and alpha-synuclein toxicity in multiple models of Parkinson’s disease.

https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-017-0456-2 

Patent portfolio

Patent


Status


Invention


“8-Hydroxyquinoline Derivatives”

Filed: July 16, 2003
Applicant: Prana Biotechnology Limited

Patents in Europe, the USA, New Zealand, Canada, Japan, Russia, Singapore, South Korea, Australia, Israel, China, Mexico and South Africa have been Granted. A patent in Hong Kong has been registered.

The invention is directed to chemical scaffolds of the 8-Hydroxyquinoline MPAC class and their utility in the treatment of neurological conditions.

“Neurologically-Active Compounds”

Filed: October 3 , 2003
Applicant: Prana Biotechnology Limited

Patents in the USA, New Zealand, Canada, Japan, Mexico, India, Australia, China, South Korea, Japan, Israel, South Africa and Singapore have been Granted. A case has been Granted in Europe and has been validated in separate countries. A patent in Hong Kong has been registered.

The invention is directed to alternative MPAC chemical structures and their utility in the treatment of neurological conditions.

“Neurologically- Active Compounds”

Filed: April 1, 2005
Applicant: Prana Biotechnology Limited

Patents have been Granted in Singapore, Japan, Mexico, Russia, Australia, the USA, China, Canada, Europe, India, South Korea, Israel, New Zealand and South Africa. A case has been Granted in Europe and has been validated in separate countries. A patent in Hong Kong has been registered.

The invention is directed to ‘F4’ MPAC chemical structures and their utility in the treatment of neurological conditions and includes Parkinson’s disease lead compounds.

“A method of prophylaxis or treatment and agents for same”

Filed: June 22, 2007
Applicant: Prana Biotechnology Limited

A patent has been Granted in the USA, China, Australia, Canada and Japan. A case has been Granted in Europe and has been validated in separate countries.

This invention is directed to novel MPAC compounds and compounds for treating certain brain cancers.

“Quinazolinone compounds”

Filed: 24 December 2008
Applicant: Prana Biotechnology Limited

Patents have been Granted in Japan, Australia, Europe and the USA.

This invention is directed to novel MPAC compounds and to select MPAC’s used in the treatment of Parkinson’s disease. Particularly new 2, 3 substituted F4 compounds.

“4H-Pyrido(1,2-a) Pyrimidin-4-one compounds”

Filed: 2 December 2014 (prov)
Applicant: Prana Biotechnology Limited

PCT National phase patent applications has been filed in Australia, Brazil, Canada, China, EA, EU, India, Japan, Malaysia, NZ, Korea and the USA.

This invention is directed to novel MPAC compounds for the treatment of neurodegenerative diseases. Particularly new ‘F3’ compounds.

“Method of treating immunoglobulin light chain amyloidosis”

Filed: 1 July 2016
Applicant: Prana Biotechnology Limited

A PCT patent application has been filed.

This invention is directed to the treatment of light chain amyloidosis with a known compound.

“A method of the production of 2-substituted-3H-quinazolin-4-ones-I”

Filed: 12 March 2017
Applicant: Prana Biotechnology Limited

An Australian provisional application has been refiled.

This invention is directed to synthetic routes for quinazolinone compounds.

“A method of the production of 2-substituted-3H-quinazolin-4-ones-II”

Filed: 12 March 2017
Applicant: Prana Biotechnology Limited

An Australian provisional application has been refiled.

This invention is directed to synthetic routes for quinazolinone compounds.

“Processes for the preparation of 8-Hydroxy quinoline Derivatives”

Filed: 4 January 2017
Applicant: Prana Biotechnology Limited

An Australian provisional application has been refiled.

This invention is directed to synthetic routes for 8-Hydroxyquinoline Derivatives.

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