Journal article

ATH434 Rescues Pre-motor Hyposmia in a Mouse Model of Parkinsonism

LC Beauchamp, XM Liu, LJ Vella, PA Adlard, AI Bush, DI Finkelstein, KJ Barnham

Neurotherapeutics | ELSEVIER SCIENCE INC | Published : 2022

Abstract

Hyposmia is a prevalent prodromal feature of Parkinson’s disease (PD), though the neuropathology that underlies this symptom is poorly understood. Unlike the substantia nigra, the status of metal homeostasis in the olfactory bulbs has not been characterized in PD. Given the increasing interest in metal modulation as a therapeutic avenue in PD, we sought to investigate bulbar metals and the effect of AT434 (formerly PBT434) an orally bioavailable, small molecule modulator of metal homeostasis on hyposmia in a mouse model of parkinsonism (the tau knockout (tau−/−) mouse). 5.5 (pre-hyposmia) and 13.5-month-old (pre-motor) mice were dosed with ATH434 (30 mg/kg/day, oral gavage) for 6 weeks. Anim..

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