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Table 3 Summary of the efficacy of P42 in cellular, Drosophila, and mouse R6/2 HD models

From: The P42 peptide and Peptide-based therapies for Huntington’s disease

Peptide Model Population Way of administration End point Method of evaluation Results
P42 (Arribat et al., 2013) [55] Cell culture HeLa cells (hHtt171aa-136Q) Co-transfection: polyQHtt + P42 or empty vector Htt aggregation Immunostaining; filter retardation assays Rescue = 80 %
P42TAT (Arribat et al., 2014) [61] Cell culture HeLa cells (hHtt171aa-136Q) Co-transfection: polyQHtt + P42TAT or empty vector Htt aggregation Immunostaining; filter retardation assays Rescue = 80 %
P42TAT-TAMRA provided in culture cell medium Htt aggregation Immunostaining; filter retardation assays Rescue = 90 % (P42TAT concentration dependent)
P42 (Arribat et al., 2013) [55] HD Drosophila MS-1096-Gal4; UAS-HA-hHtt171aa-138Q Genetic cross: UAS-P42 vs UAS-LacZ (neutral control) Htt aggregation Immunostaining; filter retardation assays (L3 larval salivary glands) Rescue = 80 %
GMR-Gal4; UAS- hHttex1-93Q Genetic cross: UAS-P42 vs UAS- GFP (neutral control) Eye toxicity Phenotypical comparative analysis (eyes of adult flies) Rescue = 100 %
OK6-Gal4/UAS-NPY-GFP; UAS-hHtt548aa-128Q Genetic cross: UAS-P42 vs UAS-LacZ (neutral control) Larval locomotion Locomotion (mm/min) Rescue close to 100 %
OK6-Gal4/UAS-NPY-GFP; UAS-hHtt548aa-128Q Genetic cross: UAS-P42 vs UAS-LacZ (neutral control) Axonal transport Immunostaining and live imaging to quantify different parameters of Neuropeptide Y vesicles trafficking in larval motoneurons. Recovery of the different parameters: Number of vesicles: 28 %; % of pausing: 21 %; velocity: 31 %
ELAV-Gal4; UAS-hHtt548aa-128Q Genetic cross: UAS-P42 vs UAS-LacZ (neutral control) Adult survival Mean, median, and maximal survival (days) Increased median survival (day 18 to 26); no effect on mean and maximal survival
P42TAT (Arribat et al., 2014) [61] R6/2 mice hHttex1-140Q Transmucosal daily administration of P42TAT with Aonys® water-in-oil microemulsion (600 μg/ml/kg) vs empty microemulsion at pre-symptomatic (wk2 to wk11) R6/2 and Wt mice. Motor performance Latency to fall from accelerating rotarod (weeks 6, 8, and 10) Significant amelioration compared to placebo-treated R6/2 mice
Clasping test Frequency and duration of the foot-clasping posture (twice a week at wk 7, 9, and 11) Complete rescue vs placebo-treated R6/2 and to wt mice
Weight loss Weight measure between wk8 and wk10 Significant reversion of body weight loss curve vs placebo-treated mice
Intranuclear brain aggregates; astrogliosis Immunostaining: number and size of cortical and striatal intranuclear aggregates; cortical and striatal astrocyte number Significant 50 % reduction of cortical and striatal aggregates; non significant reduction of the astrogliosis
Cerebral atrophy Lateral ventricle enlargement Rescue = 30 %
  1. Legend: to characterize Htt fragments we use the general indication HttXaa-YQ: the length of the fragment is expressed as a number X of amino acids (aa) (superimposed); the length of polyQ expansion is expressed as a number Y of Q.