Alterity Therapeutics , a biotechnology company dedicated to developing disease modifying treatments for neurodegenerative diseases, announced that data in an animal model of Multiple System Atrophy (MSA) were published in the Journal of Parkinson’s Disease. MSA is a devastating neurodegenerative disorder without approved therapy.
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The publication, entitled, “The Compound ATH434 Prevents Alpha-Synuclein Toxicity in a Murine Model of Multiple System Atrophy” describes a study evaluating the efficacy of ATH434 in genetically altered mice that develop manifestations of MSA. The investigation demonstrated that in the studied brain region, ATH434 treatment reduced both the toxic oligomeric and aggregated forms of α–synuclein, a central nervous system protein important for normal function of nerve cells. At the same time, ATH434 treatment reduced the cardinal pathology of MSA (glial cell inclusions), reduced brain iron, preserved neurons and improved motor performance. The publication concluded that ATH434 is a promising small molecule drug candidate that has potential for treating MSA. The study was led by David I. Finkelstein, Ph.D., Head of Parkinson’s Disease Laboratory at the Florey Institute of Neuroscience and Mental Health and the University of Melbourne. The full publication can be accessed here.
“These preclinical data are extremely valuable as they demonstrate our thesis that by binding and redistributing excess iron in the brain of patients with Parkinsonian disorders, we can reduce α–synuclein aggregation and oxidative stress and rescue neurons in multiple brain regions to address the underlying pathology of disease,” said David Stamler, M.D., Chief Executive Officer, Alterity. “We believe that these preclinical studies may translate to clinical benefit in patients with MSA, and we look forward to further patient evaluation in our upcoming Phase 2 clinical trial.”
Elevation in regional brain iron together with accumulation of aggregated α–synuclein are important contributors to the pathology of MSA. Previous studies with ATH434 in preclinical models of Parkinson’s disease have shown that it is brain-penetrant, reduces iron accumulation and iron-mediated redox activity, provides neuroprotection, inhibits α–synuclein aggregation and improves motor function. The compound was also well-tolerated in a first-in-human oral dosing study in healthy and older adult volunteers with a favorable, dose-dependent pharmacokinetic profile.
In this study, genetically altered, or transgenic, mice overexpress α–synuclein, develop glial cell inclusions, and manifest motor and non-motor aspects of MSA. Animals received ATH434 in food or a control diet for 4 months starting at 12 months of age. Western blot analysis was used to assess oligomeric and aggregated forms of α-synuclein levels in brain and stereology was used to quantitate the number of neurons and glial cell inclusions in the substantia nigra pars compacta.