Alterity Therapeutics has announced the award of a grant from The Michael J. Fox Foundation for Parkinson's Research to determine optimal dosing of its lead drug candidate ATH434 for Parkinson's disease (PD) based on imaging of brain iron.

The funding for US$495,000 will be used to evaluate the pharmacologic profile of ATH434 in a primate model to determine the optimal dose of ATH434 in future Parkinson's disease clinical trials.  This is the second grant that Alterity has received from The Michael J. Fox Foundation to support the development of ATH434 in PD.

Alterity Chief Executive Officer Dr David Stamler said, "The Michael J. Fox Foundation is an incredible organisation at the frontier of research and treatment innovation for Parkinson's disease, which remains incurable and affects an estimated 7-10 million people worldwide[i]."

"ATH434 targets alpha-synuclein misfolding and aggregation through the redistribution of excess labile iron, and our first indication Multiple System Atrophy (MSA) is on track to start its phase 2 clinical trial later this year. The potential to expand into other Parkinsonian disorders that implicate alpha-synuclein has always been part of our strategy and this funding allows us to take another step towards realizing a program in Parkinson's disease."

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder after Alzheimer's disease and occurs when brain cells that make dopamine, a chemical that underlies control of movement, degenerate and ultimately die. Because Parkinson's disease can cause tremor, slowness, stiffness, and problems with balance and walking, it is called a "movement disorder." But non-motor symptoms such as constipation, depression, and impaired memory can also be part of PD. It is a lifelong and progressive disease, which means that symptoms slowly worsen over time.[ii]

While available therapies can treat some symptoms, people with Parkinson's urgently need new treatments to slow or stop disease progression and improve quality of life.

Dr Werner Poewe, Professor of Neurology at the Medical University Innsbruck, Austria, said, "By targeting alpha-synuclein, ATH434 has potential to modify the course of synucleinopathies such as Parkinson's disease and MSA. 

"Aggregates of misfolded alpha-synuclein protein are widely distributed in the brains of individuals affected by these disorders, and by reducing their build-up ATH434 has potential to improve the motor and non-motor symptoms of these devastating conditions. I look forward to seeing the results from the dose optimization studies for PD clinical trials and future development in this indication." 

The project will be led by Margaret Bradbury, PhD, Vice President, Nonclinical Development, in collaboration with Daniel Claassen, MD, Associate Professor of Neurology at Vanderbilt University Medical Center and David Finkelstein, PhD, who heads the PD Research Laboratory at the Florey Institute of Neuroscience and Mental Health. 

The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson's disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson's today.

About Alterity Therapeutics Limited and ATH434

Alterity's lead candidate, ATH434 (formerly PBT434), is the first of a new generation of small molecules designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration. ATH434 has been shown to reduce abnormal accumulation of α-synuclein and tau proteins in animal models of disease by redistributing labile iron in the brain. In this way, it has potential to treat Parkinson's disease and atypical forms of Parkinsonism such as Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP).

ATH434 has been granted Orphan designation for the treatment of MSA by the US FDA and the European Commission.

About Multiple System Atrophy

Multiple System Atrophy (MSA) is a rare and rapidly progressive neurological disorder affecting adults. It has no known cause. In addition to presenting with motor symptoms like those in Parkinson's disease, individuals with MSA may also experience loss of ability to coordinate voluntary movements and impaired regulation of involuntary body functions such as blood pressure, bowel and bladder control. Most of these symptoms are not addressed by available drugs for patients with Parkinson's disease. As the condition progresses, daily activities become increasingly difficult and complications such as increased difficulty swallowing, vocal cord paralysis, progressive immobility, and poor balance become more prominent. Symptoms tend to appear after age 50 and rapidly advance, leading to profound disability. 

[i] Ref: Parkinson's Disease Statistics - Parkinson's News Today
[ii] Ref: Parkinson's 101 | Parkinson's Disease (michaeljfox.org)