@article{1da5a6330a08482599db5db819f599ee,
title = "Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression",
abstract = "Quantitation of huntingtin protein in the brain is needed, both as a marker of Huntington disease (HD) progression and for use in clinical gene silencing trials. Measurement of huntingtin in cerebrospinal fluid could be a biomarker of brain huntingtin, but traditional protein quantitation methods have failed to detect huntingtin in cerebrospinal fluid. Using micro-bead based immunoprecipitation and flow cytometry (IP-FCM), we have developed a highly sensitive mutant huntingtin detection assay. The sensitivity of huntingtin IP-FCM enables accurate detection of mutant huntingtin protein in the cerebrospinal fluid of HD patients and model mice, demonstrating that mutant huntingtin levels in cerebrospinal fluid reflect brain levels, increasing with disease stage and decreasing following brain huntingtin suppression. This technique has potential applications as a research tool and as a clinical biomarker.",
author = "Southwell, {Amber L.} and Smith, {Stephen E.P.} and Davis, {Tessa R.} and Caron, {Nicholas S.} and Villanueva, {Erika B.} and Yuanyun Xie and Collins, {Jennifer A.} and {Li Ye}, Min and Aaron Sturrock and Leavitt, {Blair R.} and Schrum, {Adam G.} and Hayden, {Michael R.}",
note = "Funding Information: The authors thank Mark Wang, Jason Yao, and Mahsa Amirabassi for excellent animal care, Qingwen Xia for assistance with genotyping, Christopher Kay and Niels Skotte for assistance with antisense oligonucleotide design, Shaun Sanders for providing nestin Cre mice backcrossed 10 generations to the FVB background strain, and Paula Dietrich of the University of Tennessee Health Science Center for the generous gift of conditional HTT knockout mouse forebrain tissue. This work was supported by grants from the Canadian Institutes of Health Research (CIHR: MOP-84438 to M.R.H.), the National Institutes of Health (R01GM103841 to A.G.S. and K99MH102244 to S.E.P.S.), and postdoctoral fellowships for A.L.S. from CIHR, the Huntington Society of Canada, and the Michael Smith Foundation for Health Research. M.R.H. is a University Killam Professor and the Canada Research Chair in Human Genetics and Molecular Medicine.",
year = "2015",
month = jul,
day = "15",
doi = "10.1038/srep12166",
language = "English (US)",
volume = "5",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}