We got very corresponding results last year, but the company told us only in January. That study was done in a mouse model; today we have it in a primate model. Even the abstract of that paper a year ago gives more than the poster today: reduction of alpha-synuclein and reduction of neurodegeneration. But evidently, there will be one day a real scientific paper, and perhaps many of them. Finkelstein has been interested in gastro symptoms and eye problems and they are equally interesting in a primate model. Maybe Dr. Kosman finds also something to report on the mitochondrion level of why ATH434 works in these animal models.

Here is the abstract of that old paper (published here over a year ago.

Neurotherapeutics

. 2022 Oct;19(6):1966-1975.

doi: 10.1007/s13311-022-01300-0. Epub 2022 Sep 29.

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

PMCID: PMC9723006 DOI: 10.1007/s13311-022-01300-0Free PMC article

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.