Table 1 Previous studies of Anle138b efficacy and mechanism of action (MoA) in Alzheimer’s disease

Wagner et al. [6]

In vivo:

Transgenic PS19 mice (frontotemporal dementia model, tau mutation), administration from weaning

In vitro:

(a) Isolated and purified hTau46 cell-free tau aggregation assay

(b) Treated primary neurons

Decreased tau aggregation

Increased survival time

Improved cognition

Decreased synapse and neuron loss

Reduced hippocampal gliosis and neuroinflammation

Decreased tau aggregation

None

No change in activity of autophagy markers

Reduction in amount of phosphorylated tau

Change in fluorescent activity of Anle138b in presence of pre-aggregated tau

Slight but not significant increased phosphorylation of GSK3, no change in expression level or activity of PP2A

No effect on tau ubiquitination levels

Brendel et al. [7]

Transgenic mice expressing all 6 hTau isoforms, administration at late disease stage

Metabolic decline significantly reduced

Correlation of glucose metabolism with end-point tau load

Martinez Hernandez et al. [8]

Amyloid: APPPS1∆9 mice (mouse model for amyloid deposition), treatment both before onset of pathology “pre-plaque”, and after onset of deposition and memory disturbances “post-plaque”

Tau: Model as in Wagner et al

Rescue of amyloid-induced deficits in synaptic plasticity, long-term potentiation and memory formation

None

Binding to and reduction in conductivity of membrane-associated amyloid beta pores

No reduction in inflammatory gene expression disease signatures in post-plaque group

Amelioration of disease-induced inflammatory gene expression signatures

Dominguez-Meijide et al. [9]

HEK293 venus BiFC (bimolecular fluorescence complementation) cell model treated with Anle138b

Inhibition of the aggregation process and disaggregation of tau aggregates

None