ArticleJournal of Parkinson's disease2022
The Compound ATH434 Prevents Alpha-Synuclein Toxicity in a Murine Model of Multiple System Atrophy.
Article in Journal of Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Multiple system atrophy: cure and care.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Astrocytic FABP5 drives non-cell-autonomous oligodendrocyte injury in multiple system atrophy by promoting TNF signaling and ferroptotic stress.Redox biology · 2026Article
- Targeting protein disorder: the next hurdle in drug discovery.Nature reviews. Drug discovery · 2025Review
- ATH434, a promising iron-targeting compound for treating iron regulation disorders.Metallomics : integrated biometal science · 2024Article
- Retinal hyperspectral imaging in mouse models of Parkinson's disease and healthy aging.Scientific reports · 2024Article
- Multiple system atrophy: an update and emerging directions of biomarkers and clinical trials.Journal of neurology · 2024Review
- Recent Advances in Clinical Trials in Multiple System Atrophy.Current neurology and neuroscience reports · 2024Review
- Pharmacological inhibition of FABP7 by MF 6 counteracts cerebellum dysfunction in an experimental multiple system atrophy mouse model.Acta pharmacologica Sinica · 2024Article
- Impaired skeletal muscle health in Parkinsonian syndromes: clinical implications, mechanisms and potential treatments.Journal of cachexia, sarcopenia and muscle · 2023Review
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- Kathrin Brockmann, Milan Zimmermann, and Dareia Roos, Recipients of The Parkinson Prize 2023.Journal of Parkinson's disease · 2023Article
- Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies.International journal of molecular sciences · 2022Review
- Alpha-Synuclein Targeting Therapeutics for Parkinson's Disease and Related Synucleinopathies.Frontiers in neurology · 2022Review
- Aberrant Cerebral Iron Trafficking Co-morbid With Chronic Inflammation: Molecular Mechanisms and Pharmacologic Intervention.Frontiers in neurology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAn elevation in iron levels, together with an accumulation of α-synuclein within the oligodendrocytes, are features of the rare atypical parkinsonian disorder, Multiple System Atrophy (MSA). We have previously tested the novel compound ATH434 (formally called PBT434) in preclinical models of Parkinson's disease and shown that it is brain-penetrant, reduces iron accumulation and iron-mediated redox activity, provides neuroprotection, inhibits alpha synuclein aggregation and lowers the tissue levels of alpha synuclein. The compound was also well-tolerated in a first-in-human oral dosing study in healthy and older volunteers with a favorable, dose-dependent pharmacokinetic profile.
objectiveTo evaluate the efficacy of ATH434 in a mouse MSA model.
methodsThe PLP-α-syn transgenic mouse overexpresses α-synuclein, demonstrates oligodendroglial pathology, and manifests motor and non-motor aspects of MSA. Animals were provided ATH434 (3, 10, or 30 mg/kg/day spiked into their food) or control food for 4 months starting at 12 months of age and were culled at 16 months. Western blot was used to assess oligomeric and urea soluble α-synuclein levels in brain homogenates, whilst stereology was used to quantitate the number of nigral neurons and glial cell inclusions (GCIs) present in the substantia nigra pars compacta.
resultsATH434 reduced oligomeric and urea soluble α-synuclein aggregation, reduced the number of GCIs, and preserved SNpc neurons. In vitro experiments suggest that ATH434 prevents the formation of toxic oligomeric "species of synuclein".
conclusionATH434 is a promising small molecule drug candidate that has potential to move forward to trial for treating MSA.
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