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. 2021 Feb;36(2):492-497.
doi: 10.1002/mds.28300. Epub 2020 Oct 2.

Cerebrospinal Fluid Levels of Prodynorphin-Derived Peptides are Decreased in Huntington's Disease

Mhd Rami Al Shweiki  1 , Patrick Oeckl  1 , Adrian Pachollek  1 , Petra Steinacker  1 , Peggy Barschke  1 , Steffen Halbgebauer  1 , Sarah Anderl-Straub  1 , Jan Lewerenz  1 , Albert C Ludolph  1   2 , Georg Bernhard Landwehrmeyer  1 , Markus Otto  1
Affiliations

Cerebrospinal Fluid Levels of Prodynorphin-Derived Peptides are Decreased in Huntington's Disease

Mhd Rami Al Shweiki et al. Mov Disord. 2021 Feb.

Abstract

Results: 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.

Results: 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).

Results: 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.

Conclusions: 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.

Keywords: neurofilaments; prodynorphin; biomarker; Huntingtonʼs disease; frontotemporal dementia.

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