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
Neurofilament Light Chain and Clinical Progression in Early Multiple System Atrophy
Effects of ATH434, a Clinical-phase Small Molecule with Moderate Affinity for Iron, in a Parkinson’s Disease Model in Macaubes
ATH434 Rescues Pre-motor Hyposmia in a Mouse Model of Parkinsonism
ATH434 protects brain cells and improves motor function – Alterity Therapeutics
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.