Abstract
Huntington's disease (HD) is a devastating neurodegenerative disorder characterized by a selective loss of striatal medium spiny projection neurons (MSNs). Prodynorphin (PDYN) is enriched in a subpopulation of striatal MSNs. Postmortem brains of HD patients and rodent models have been demonstrated to have reduced levels of PDYN transcripts and the neuropeptide dynorphin. Given the unmet need for novel pharmacodynamic HD biomarkers in the context of experimental huntingtin (htt)-lowering therapies, we investigated the levels of PDYN-derived peptides and neurofilament light (NfL) chain in the cerebrospinal fluid (CSF) from HD patients (n = 16), matched controls (n = 55), and patients with other neurodegenerative disorders (n = 70). PDYN-derived peptide levels were found to be substantially decreased in HD patients (P < 0.0001 in comparison to controls), whereas the NfL levels were elevated in all neurodegenerative disorders. Our study suggests decreased PDYN-derived peptide levels in the CSF as a more specific biomarker for HD in comparison to NfL. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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