Do Mouse Data Lie? For Buntanetap, They Totally Predict Human Outcome

Abstract

AbstractBackgroundOverexpression of neurotoxic proteins drives downstream events that dysregulate axonal transport, lead to inflammation, nerve cell death, and loss of function (Chen et al. 2021). By inhibiting the translation of neurotoxic aggregating proteins ‐ amyloid precursor protein, tau, alpha‐synuclein etc., buntanetap restores axonal transport, lowers inflammation, and protects nerve cells from dying. In three double‐blind, placebo controlled, phase 1/2 clinical studies in both Alzheimer (AD) and Parkinson (PD) patients buntanetap showed statistically significant improvement in movement in PD and cognition in AD (Fang et al. 2023).MethodHere we want to compare our animal data with our human data to evaluate if animal models are predictive of human outcomes. We are comparing data from APP/PS1 AD mice (Teich et al. 2018), Ts65Dn Down Syndrome mice (Chen et al. 2020), and two Phase 1 /2 double‐blind, placebo‐controlled human AD studies: Discover study run by ADCS and AD/PD study run by Annovis.Result1. Buntanetap is a translational inhibitor of APP by pulse‐chase experiment in mice and by stable isotope labeling kinetics (SILK) in humans (Galasko et al. 2022).2. Our drug inhibits APP/Abeta, tau/pTau in a dose‐dependent manner in animals (Lahiri et al. 2007; Teich et al. 2018; Chen et al. 2020) and humans (Maccecchini et al. 2012).3. The biomarker dose‐response is seen at a much higher dose than the efficacy dose‐response.4. We see a statistical improvement in cognition in animals and in humans (Teich et al. 2018; Fang et al. 2023).ConclusionIn all our studies conducted to date in AD mice and humans, we have obtained consistent data on the mechanism of action, consistently lowered levels of neurotoxic aggregating proteins, and consistent improvements in cognition.