Skip to main content

Table 1 Summary of the efficacy of the different peptides against HD

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

Peptide Target of the peptide Model Population Way of administration End point Method of evaluation Results
Bivalent Htt-binding peptide (Kazantsev et al., 2002) [31] PolyQ stretches Cell culture COS-1 cells Co-transfection of hHtt17aa-103Q ± bivalent Htt-binding peptide Aggregation % of aggregate-positive transfected cells Delayed aggregate formation: 37.6 % reduction at 48 h; no reduction at 96 h
Drosophila HD ELAV-Gal4; UAS- 48/108Q Genetic cross: bivalent Htt-binding peptide vs placebo Survival Survival rate Significant increased survival
Aggregation (CNS) Immunostaining on L3 larvae Significant aggregate reduction
GMR-Gal4; UAS- 48/108Q Genetic cross: bivalent Htt-binding peptide vs placebo Photoreceptor neurodegeneration Quantification of the number of rhabdomeres/ommatidium Significant rescue of eye neurodegeneration
Polyglutamine-binding peptide 1 (QBP1) (Nagai et al., 2000) [32] Expanded polyQ stretch Cell culture COS-7 cells Co-transfection of 45Q-/57Q-/81Q-YFP ± QBP1-CFP Aggregation % of aggregate-positive transfected cells Significant aggregate reduction, more important with shorter polyQ
(QBP1)2 (Nagai et al., 2003) [33] Expanded polyQ stretch Drosophila polyQ models GMR-92Q Genetic cross: Eyeless-Gal4; UAS-(QBP1)2 or GMR-Gal4; UAS-(QBP1)2 Photoreceptor neurodegeneration Phenotypical comparative analysis (adult flies) Significant suppression of eye degeneration
GMR-Gal4; UAS-MJDtr-78Q Genetic cross: UAS-(QBP1)2 Photoreceptor neurodegeneration Phenotypical comparative analysis (adult flies) Significant suppression of eye degeneration
GMR-92Q Genetic cross: Eyeless-Gal4; UAS-(QBP1)2 Aggregation in the eye imaginal disc Immunostaining (third instar larvae) Significant inclusion bodies reduction
ELAV-Gal4; UAS-MJDtr-78Q Genetic cross: UAS-(QBP1)2 or UAS-(scrambled)2 Survival Life span (adult flies) Significant increase in survival (median life span from 5.5 to 52 days)
PTD-QBP1 Expanded polyQ stretch Cell culture (Popiel et al., 2007) [39] COS-7 cells Co-transfection of 81Q-GFP ± Antp-QBP1 provided in the cell medium Aggregation % of transfected cells forming inclusion bodies Significant reduction (from 42 % to 30 %)
COS-7 cells Co-transfection of 57Q-GFP ± TAT-QBP1 provided in the cell medium Cell survival Quantification of cell death Significant reduction of cell death (from 11.8 % to 7.4 %)
Drosophila polyQ model (Popiel et al., 2007) [39] ELAV-Gal4; UAS-MJDtr-78Q Oral administration of Antp-QBP1 Survival Survival rate (5,10, and 15 days) Significant increase
   Aggregation in the eye imaginal disc Immunostaining (third instar larvae) Significant reduction of inclusion bodies
Mouse model (Popiel et al., 2009) [40] R6/2 mice Long-term continuous intraperitoneal administration of either Antp-QBP1 (2 mg/week) or saline from wk2 Motor performances Latency to fall with accelerating rotarod (from wk5 to death) No significant difference
Body weight Weight measure (from wk5 to death) Significant weight increased compared to saline-treated mice from wk5 to 10
Survival Life span No significant difference
Long-term continuous intraperitoneal administration of either Antp-QBP1 (2 mg/week) or saline from wk2 Aggregation Brain section immunostaining with anti-htt antibody No significant difference
ED11 (Aharony et al., 2015) [41] Inhibitor of caspase-6 Cell culture PC12 cells Inducible mHtt- 145Q ± TAT-ED11 provided in the cell medium Survival Cell viability and cell death assessment Significant increased cell viability and decreased cell death
Mouse model Full-length hHtt-97Q BACHD Pre-symptomatic treatment (from wk5); continuous infusion (4 mg/kg/day; subcutaneously implanted mini-pump) of ED11 peptide vs vehicle in BACHD mice and of vehicle in wt mice Body weight (excessive weight) Weight measure Attenuation of weight gain
Motor performances Latency to fall with accelerating rotarod (monthly from wk9) Preserved motor performance compared to wt mice.
Depressive-like behaviour Immobility evaluation during the forced swim test (FST) (5 months of age) Prevention of increased immobility
Basal locomotor activity, exploratory activity, anxiety-related behaviour Open field test (wk22): total travelled distance; time spent in the centre and number of transitions to the centre Unchanged basal locomotor activity; lower anxiety levels and improved exploratory behaviour in treated vs untreated mice
Inhibition of caspase-6 activity Quantification of mHtt586aa fragments (6-month-old mice) Not evaluable (no detectable mHtt586aa fragments in untreated mice)
Aggregation Immunostaining (6-month-old mice) Not evaluable (no detectable aggregates in untreated mice)
Post-symptomatic treatment (from w36); continuous infusion (4 mg/kg/day; subcutaneously implanted mini-pump) of ED11 peptide vs vehicle in BACHD mice and of vehicle in wt mice Motor performances Latency to fall with accelerating rotarod (monthly, wk30 to 44) Increased motor performance compared to untreated mice
Depressive-like behaviour Immobility evaluation during the forced swim test (FST) (11 months of age) Rescue at the level of wt littermates
Cognitive deficits Swimming T-maze test; shifting abilities (time to reach the re-located hidden platform) Rescue at the level of wt littermates
Brain atrophy MRI volumetric measurements (12 months of age) Not evaluable (no significant atrophy in untreated BACHD mice)
  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.