Publication
Title
Development of a ligand for in vivo imaging of mutant huntingtin in Huntington’s disease
Author
Abstract
Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene that encodes the pathologic mutant HTT (mHTT) protein with an expanded polyglutamine (polyQ) tract. Whereas several therapeutic programs targeting mHTT expression have advanced to clinical evaluation, methods to visualize mHTT protein species in the living brain are lacking. Here, we demonstrate the development and characterization of a positron emission tomography (PET) imaging radioligand with high affinity and selectivity for mHTT aggregates. This small molecule radiolabeled with 11C ([11C]CHDI-180R) allowed noninvasive monitoring of mHTT pathology in the brain and could track region- and time-dependent suppression of mHTT in response to therapeutic interventions targeting mHTT expression in a rodent model. We further showed that in these animals, therapeutic agents that lowered mHTT in the striatum had a functional restorative effect that could be measured by preservation of striatal imaging markers, enabling a translational path to assess the functional effect of mHTT lowering.
Language
English
Source (journal)
Science translational medicine. - -
Publication
2022
ISSN
1946-6234
DOI
10.1126/SCITRANSLMED.ABM3682
Volume/pages
14 :630 (2022)
Article Reference
eabm3682
ISI
000750219600006
Pubmed ID
35108063
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Preclinical PET imaging of allele-selective mHTT lowering as candidate treatment for Huntington's Disease.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identifier
Creation 03.03.2022
Last edited 03.10.2024
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