Quantifying mutant huntingtin protein in human cerebrospinal fluid to support the development of huntingtin-lowering therapies.

ABSTRACT: Huntington's disease (HD) is caused by a cytosine adenine guanine-repeat expansion in the huntingtin gene. This results in the production of toxic mutant huntingtin protein (mHTT), which has an elongated polyglutamine (polyQ) stretch near the protein's N-terminal end. The pharmacological lowering of mHTT expression in the brain targets the underlying driver of HD and is one of the principal therapeutic strategies being pursued to slow or stop disease progression. This report describes the characterisation and validation of an assay designed to quantify mHTT in the cerebrospinal fluid of individuals with HD, for use in registrational clinical trials. The assay was optimised, and its performance was characterised with recombinant huntingtin protein (HTT) varying in overall and polyQ-repeat l

SUBMITTER: Vauleon S 

PROVIDER: S-EPMC10067853 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature