Alterity announces presentations of data on Parkinson’s Disease, MSA

Alterity Therapeutics announced that three posters were presented at the American Academy of Neurology 2024 Annual Meeting taking place April 13-18, 2024, in Denver, Colorado, USA. Featured presentations described the Company’s work in Parkinson’s disease and Multiple System Atrophy, including initial biomarker data and baseline characteristics from the ATH434-201 Phase 2 clinical trial. Presentation Summaries: Title: A Phase 2 Study of ATH434, a Novel Inhibitor of alpha-Synuclein Aggregation, for the Treatment of Multiple System Atrophy. Results: The poster describes the baseline characteristics for the 65 evaluable participants from Alterity’s ATH434-201 randomized, double-blind Phase 2 clinical trial, with a focus on baseline fluid biomarkers, neuroimaging and clinical data. The participants met the strict criteria designed to confirm that participants were diagnosed with early-stage MSA and had a mean of two years of motor symptoms. ATH434 is a potential disease modifying therapy based on its ability to redistribute excess labile iron without impairing normal iron storage, inhibit alpha-synuclein aggregation and reduce oxidative stress. Importantly, the increased iron levels in the trial participants were evident in multiple subcortical brain regions with two distinct patterns of iron accumulations observed. In addition, MSA participants with less than four years of motor symptoms have elevated plasma Neurofilament Light Chain levels at baseline which correlate significantly with disease severity. Title: Neurofilament Light Chain and Clinical Progression in Early Multiple System Atrophy. Results: The poster describes results from the bioMUSE Natural History Study in which changes in clinical severity of 15 patients across a span of 12 months were compared with plasma biomarkers with a goal of establishing meaningful correlations. The advancement of MSA is profoundly aggressive, highlighting the critical need for biomarkers to delineate its progression over time. Emerging interest surrounds the use of the fluid biomarker NfL, found in both cerebrospinal fluid and plasma, as an indicator of axonal damage in MSA. This fluid biomarker holds promise for measuring the extent of disease, tracking its progression, and forecasting the onset of clinical manifestations associated with MSA. In this observational study, the plasma NfL and CSF NfL were highly correlated, indicating that the more easily obtained plasma values have a meaningful relationship with brain pathology. Plasma NfL significantly increased over 12 months, and both plasma and CSF NfL were associated with disease progression in MSA. These data suggest that NfL may be a marker of disease modification in studies of MSA. Title: Effects of ATH434, a Clinical-Phase Small Molecule with Moderate Affinity for Iron, in Hemiparkinsonian Macaques. Results: The presentation demonstrated that ATH434 treatment led to lower iron levels in the affected area of the brain, the substantia nigra, and improved motor performance and general function in monkeys with experimentally induced Parkinson’s disease. At week 12, all 6 ATH434-treated macaques had stable or improving scores from Baseline while two of three vehicle-treated macaques did not demonstrate improvement. The improved general behavior was well-correlated with reduced motor impairment. These favorable parkinsonian outcomes observed in each of the ATH434-treated monkeys were also associated with increased levels of striatal synaptophysin, a protein marker that reflects functional connections between neurons, suggesting functional recovery of nerve endings in this critical motor pathway. These results support further investigation of ATH434 for the treatment of Parkinson’s disease.