Optimal HAEE synthetic peptide therapeutic dose with repeated administration to APP/PS1 mice

High efficacy of the synthetic Ac-His-Ala-Glu-Glu-NH2 (HAEE) peptide in suppression of the congophilic amyloid plaque formation was earlier shown in the animal model of Alzheimer's disease. The study conducted as part of the pre-clinical trial aimed to determine the optimal therapeutic dose of this peptide when used as an anti-amyloid agent for treatment of this disorder. The APP/PS1 transgenic mice randomized into four experimental groups and one control group (eight males and eight females per group) were used as model animals. Mice of experimental groups 1, 2, 3, and 4 twice a week throughout eight weeks received subcutaneous injections of drugs with the following HAEE dosage: 0.18 mg/kg, 0.30 mg/kg, 1.50 mg/kg, 3.00 mg/kg. Mice of the control group were administered saline. The Congo red stain was used to determine amyloid plaques in the hippocampus of all animals. Quantification of such plaques showed a significant (p < 0.001) decrease in the number of plaques in mice of experimental groups (the average plaque number per brain slice was 7.5 ± 2.1, 3.2 ± 0.9, 3.1 ± 0.6, and 3.3 ± 0.7 in mice of groups 1, 2, 3, and 4, respectively) compared to control mice (15.7 ± 4.6). Since the number of plaques in groups 2, 3, and 4 did not change significantly, the minimal HAEE dose, with which the lowest number of amyloid plaques is observed in the studied mice, is 0.3 mg/kg. This is roughly equivalent to the dose of 1.75 mg in terms of one adult human. Thus, the optimal therapeutic HAEE dose for clinical trials has been experimentally substantiated.