biostudies-literatureBirolini GTelethon106823https://www.ebi.ac.uk/biostudies/studies/S-EPMC10463277biostudies-literatureUnknown194Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing ("early treatment") or reversing ("late treatment") HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic ("early treatment") or symptomatic ("late treatment") stages iPharmacological researchChronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease.PMC10463277GGP17102Favagrossa MRuozi BTrucco ACappelleri AMinoli LOttonelli ITalpo FBiella GPassoni ANucera MRBagnati RCaraffi RPaltrinieri STaroni FScanziani ECanevari CBirolini GLeoni VCaccia CVandelli MADuskey JTValenza MTosi GSalmona MColombo LBombaci MCattaneo EfalseChronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease.Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing ("early treatment") or reversing ("late treatment") HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally. We show that one cycle of treatment with hybrid-g7-NPs-chol, administered in the presymptomatic ("early treatment") or symptomatic ("late treatment") stages i2023-01-01T00:00:00Z2023 Aug2026-06-05T06:59:26.708Z2025-04-04T19:24:08.638ZS-EPMC104632773733643010.1016/j.phrs.2023.106823