Al Shweiki Mhd Rami, Oeckl Patrick, Pachollek Adrian, Steinacker Petra, Barschke Peggy, Halbgebauer Steffen, Anderl-Straub Sarah, Lewerenz Jan, Ludolph Albert C, Bernhard Landwehrmeyer Georg, Otto Markus
Department of Neurology, Ulm University Hospital, Ulm, Germany.
German Center for Neurodegenerative Diseases, Ulm, Germany.
Mov Disord. 2021 Feb;36(2):492-497. doi: 10.1002/mds.28300. Epub 2020 Oct 2.
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.
亨廷顿舞蹈症（HD）是一种毁灭性的神经退行性疾病，其特征是纹状体中等棘状投射神经元（MSN）选择性丧失。前强啡肽原（PDYN）在纹状体MSN的一个亚群中富集。已证实HD患者和啮齿动物模型的尸检大脑中PDYN转录本和神经肽强啡肽水平降低。
鉴于在实验性降低亨廷顿蛋白（htt）疗法的背景下对新型药效学HD生物标志物的需求尚未得到满足，我们研究了HD患者（n = 16）、匹配的对照组（n = 55）和其他神经退行性疾病患者（n = 70）脑脊液（CSF）中PDYN衍生肽和神经丝轻链（NfL）的水平。
发现HD患者中PDYN衍生肽水平显著降低（与对照组相比，P < 0.0001），而在所有神经退行性疾病中NfL水平均升高。
我们的研究表明与NfL相比，脑脊液中PDYN衍生肽水平降低是HD更具特异性的生物标志物。© 2020作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
