Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification.

ABSTRACT: Huntington disease (HD) is a progressive and devastating neurodegenerative disease caused by expansion of a glutamine-coding CAG tract in the huntingtin (HTT) gene above a critical threshold of ~35 repeats resulting in expression of mutant HTT (mHTT). A promising treatment approach being tested in clinical trials is HTT lowering, which aims to reduce levels of the mHTT protein. Target engagement of these therapies in the brain are inferred using antibody-based assays to measure mHTT levels in the cerebrospinal fluid (CSF), which is frequently reported as absolute mHTT concentration based on a monomeric protein standard used to generate a standard curve. However, patient biofluids are a complex milieu of different mHTT protein species, suggesting that absolute quantitation is challen

SUBMITTER: Harding RJ 

PROVIDER: S-EPMC11463412 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature