Anle138b ameliorates pathological phenotypes in mouse and cellular models of Huntington's disease

ABSTRACT: Huntington's disease (HD) is a hereditary movement disorder caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by deposition of mutant huntingtin (mHTT) aggregates, and by severe neurodegeneration of the basal ganglia and neocortex. No cure is currently available, and new treatment options are urgently needed. Here, we show that the oligomer modifying molecule anle138b (INN: emrusolmin) improves multiple disease phenotypes in cell culture and in two mouse models of HD. Application of anle138b reduced mHTT aggregate formation and ameliorated neurotoxicity in primary neurons. Oral administration of anle138b delayed deposition of mHTT inclusions, reduced brain atrophy, mitigated neuroinflammation and transcriptional alterations, improved motor function and extended l

SUBMITTER: Miguel da Silva Padilha 

PROVIDER: S-SCDT-10_1038-S44321-026-00459-9 | biostudies-other |

REPOSITORIES: biostudies-other