Abstract Details

Title Evaluation of mutant huntingtin and neurofilament proteins as potential markers in Huntington’s disease

Topic Movement Disorders

Presentation(s) S16 - Huntington's Disease: From Bench to Clinical Trials (1:22 PM-1:33 PM)

Poster/Presentation
Number 003

Objective To assess mutant huntingtin (mHTT) and neurofilament light (NfL) in parallel in Huntington’s disease (HD).

Background

HD is a progressive neurodegenerative disorder where there is a pressing need for sensitive biomarkers.

Design/Methods CSF mHTT, CSF NfL and plasma NfL were measured using immunoassays in 80 participants (20 healthy controls, 20 premanifest HD and 40 manifest HD) underwent clinical assessments, and standardized CSF and blood collections. Analysis included multiple linear regression models, Pearson’s correlations, receiver operating characteristics curves and samples sizes calculations. An event-based model was used to assess the temporal sequence of HD-related biomarker alterations.

Results CSF mHTT, CSF NfL and plasma NfL were significantly higher as disease progressed and associated with all clinical measures. Both CSF and plasma NfL were associated with brain volume measures, but CSF mHTT was not. CSF mHTT, CSF NfL and plasma NfL were closely correlated, and highly stable within individuals. CSF mHTT had perfect accuracy for distinguishing between controls and HD mutation carriers, and both CSF and plasma NfL had excellent accuracy for distinguishing between premanifest and manifest HD. Sample size calculations suggest low participant numbers needed to incorporate these measures into clinical trials. The biofluid biomarkers emerged as the earliest detectable alterations in HD, followed by brain volume, motor and cognitive measures.

Conclusions In this cross-sectional study we provide evidence to support mHTT and NfL as having favourable properties as biofluid biomarkers for HD. Our data suggests that these key biofluid biomarkers are some of the earliest detectable changes in HD.

Authors/Disclosures
Filipe A. Brogueira Rodrigues PRESENTER	No disclosure on file
	No disclosure on file
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	No disclosure on file
Christian Czech, PhD	No disclosure on file
Scott Schobel	Scott Schobel has received personal compensation for serving as an employee of F. Hoffman-La Roche Ltd.
	No disclosure on file
	No disclosure on file
Henrik Zetterberg (Sahlgrenska University Hospital/Molndal)	Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche, and WebMD. Henrik Zetterberg has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley and Elsevier. Henrik Zetterberg has stock in Brain Biomarker Solutions.
Edward J. Wild, MBBS, PhD, MRCP (UCL Institute of Neurology)	Dr. Wild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alnylam. Dr. Wild has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Skyhawk Therapeutics. Dr. Wild has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Ionis Pharmacauticals. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Life Sciences. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman La Roche. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vico Therapeutics. Dr. Wild has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PTC Therapeutics. The institution of Dr. Wild has received research support from CHDI Foundation (non-profit).

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