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PET Ligands for Imaging Mutant Huntingtin Aggregates: A Case Study in Non-For-Profit Scientific Management

Accepted version
Peer-reviewed

Type

Article

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Authors

Dickmann, Catherine 
Milicevic Sephton, S 
Barker, RA 
Aigbirhio, FI 

Abstract

Positron emission tomography of proteinopathies with high-affinity and selective radioligands has played a vital role in expanding our knowledge of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. The pathogenesis of Huntington’s disease, a CAG trinucleotide repeat disorder, is similarly linked to the presence of protein fibrils formed from mutant huntingtin (mHTT). Development of mHTT fibril-specific radioligands has been limited by the lack of structural knowledge around mHTT and a dearth of available hit compounds for medicinal chemistry refinement. Over the past decade, the Cure Huntington’s Disease Initiative (CHDI), a non-for-profit scientific management organisation has orchestrated a large-scale screen of small molecules to identify high affinity ligands of mHTT, with lead compounds now reaching clinical maturity. Here we describe the mHTT radioligands developed to date and opportunities for further improvement of this radiotracer class.

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Keywords

Journal Title

ChemBioChem

Conference Name

Journal ISSN

1439-4227
1439-7633

Volume Title

Publisher

Wiley-VCH Verlag