This may be reposting but at least I have not noticed the company tell about this study done by the old "Prana team". There are not too many ATH434 papers published but now it looks like there are more of them done in PD models (3) than in MSA models (2).

So if you lose your smelling sense, better to take ATH434 to avoid developing other signs of PD. Let us hope this will become real one day.

Neurotherapeutics

. 2022 Sep 29.

doi: 10.1007/s13311-022-01300-0. Online ahead of print.

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

Leah C Beauchamp ^{1 2}, Xiang M Liu ¹, Laura J Vella ^{1 2 3}, Paul A Adlard ^{1 2}, Ashley I Bush ^{1 2}, David I Finkelstein ^{1 2}, Kevin J Barnham ^{4 5}

Affiliations expand

• PMID: 36175781

DOI: 10.1007/s13311-022-01300-0

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. Animals then underwent behavioral analysis for olfactory and motor phenotypes. The olfactory bulbs and the substantia nigra were then collected and analyzed for metal content, synaptic markers, and dopaminergic cell number. ATH434 was able to prevent the development of hyposmia in young tau^-/- mice, which coincided with a reduction in bulbar iron and copper levels, an increase in synaptophysin, and a reduction in soluble α-synuclein. ATH434 was able to prevent the development of motor impairment in aged tau^-/- mice, which coincided with a reduction in iron levels and reduced neurodegeneration in the substantia nigra. These data implicate metal dyshomeostasis in parkinsonian olfactory deficits, and champion a potential clinical benefit of ATH434 in both prodromal and clinical stages of PD.