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.
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 HDpatients 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 HDpatients (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 HDpatients (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.
Authors: Michael Benatar; Joanne Wuu; Caroline McHutchison; Ronald B Postuma; Bradley F Boeve; Ronald Petersen; Christopher A Ross; Howard Rosen; Jalayne J Arias; Stephanie Fradette; Michael P McDermott; Jeremy Shefner; Christine Stanislaw; Sharon Abrahams; Stephanie Cosentino; Peter M Andersen; Richard S Finkel; Volkan Granit; Anne-Laure Grignon; Jonathan D Rohrer; Corey T McMillan; Murray Grossman; Ammar Al-Chalabi; Martin R Turner Journal: Brain Date: 2022-03-29 Impact factor: 15.255
Authors: Peggy Barschke; Samir Abu-Rumeileh; M H D Rami Al Shweiki; Lorenzo Barba; Federico Paolini Paoletti; Patrick Oeckl; Petra Steinacker; Steffen Halbgebauer; Lorenzo Gaetani; Jan Lewerenz; Albert Christian Ludolph; Georg Bernhard Landwehrmeyer; Lucilla Parnetti; Markus Otto Journal: J Neurol Date: 2022-06-23 Impact factor: 6.682