Alterity Therapeutics Limited announced that a study recently published in the journal Neurotherapeutics demonstrated that its lead clinical asset, ATH434, was neuroprotective in a genetic model of Parkinson's disease (PD). Parkinson's is a progressive neurodegenerative disorder that causes slow or abnormal movements of the body and non-motor features that contribute significantly to morbidity and reduced quality of life. The publication, entitled "ATH434 Rescues Premotor Hyposmia in a Mouse Model of Parkinsonism" assessed the impact of ATH434 on motor and non-motor deficits in mice with genetically induced Parkinson's disease1.

Hyposmia, defined as reduced sensitivity to odor, is an early and common non-motor symptom of PD that precedes the typical motor symptoms by several years, occurring in approximately 90% of early-stage cases of PD2. The study found that ATH434 prevented a loss of smell in the younger mice and rescued it in older mice. More importantly, the authors also demonstrated that ATH434 prevented the development of motor impairment in older animals, which was associated with a reduction in iron levels and preservation of neurons in the substantia nigra, the brain region affected in Parkinson's. These data support other studies indicating that ATH434 has a beneficial effect on the motor and non-motor symptoms in animal models of PD.

Alterity's lead candidate, ATH434, is an oral agent designed to inhibit the aggregation of pathological proteins implicated in neurodegeneration. ATH434 has been shown preclinically to reduce -synuclein pathology and preserve nerve cells by restoring normal iron balance in the brain. As an iron chaperone, it has excellent potential to treat Parkinson's disease as well as various Parkinsonian disorders such as Multiple System Atrophy (MSA).

ATH434 successfully completed Phase 1 studies demonstrating the agent is well tolerated and achieved brain levels comparable to efficacious levels in animal models of MSA. ATH434 is currently being studied in a randomized, double-blind, placebo-controlled Phase 2 clinical trial in patients with early-stage MSA. ATH434 has been granted Orphan designation for the treatment of MSA by the U.S. FDA and the European Commission.