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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Cathepsin D as biomarker in cerebrospinal fluid of nusinersen-treated patients with spinal muscular atrophy
European Journal of Neurology, Volume 29, No. 7, Year 2022
Notification
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Description
Background and purpose: The therapeutic landscape of spinal muscular atrophy (SMA) has changed dramatically during the past 4 years, but treatment responses differ remarkably between individuals, and therapeutic decision-making remains challenging, underlining the persistent need for validated biomarkers. Methods: We applied untargeted proteomic analyses to determine biomarkers in cerebrospinal fluid (CSF) samples of SMA patients under treatment with nusinersen. Identified candidate proteins were validated in CSF samples of SMA patients by Western blot and enzyme-linked immunosorbent assay. Furthermore, levels of peripheral neurofilament heavy and light chain were determined. Results: Untargeted proteomic analysis of CSF samples of three SMA type 1 patients revealed the lysosomal protease cathepsin D as a candidate biomarker. Subsequent validation analysis in a larger cohort of 31 pediatric SMA patients (type 1, n = 12; type 2, n = 9; type 3, n = 6; presymptomatically treated, n = 4; age = 0–16 years) revealed a significant decline of cathepsin D levels in SMA patients aged ≥2 months at the start of treatment. Although evident in all older age categories, this decline was only significant in the group of patients who showed a positive motor response. Moreover, downregulation of cathepsin D was evident in muscle biopsies of SMA patients. Conclusions: We identified a decline of cathepsin D levels in CSF samples of SMA patients under nusinersen treatment that was more pronounced in the group of "treatment responders" than in "nonresponders." We believe that our results indicate a suitability of cathepsin D levels as a possible biomarker in SMA also in older patients, in combination with analysis of peripheral neurofilament light chain in adolescents or alone in adult patients. © 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Authors & Co-Authors
Schorling, David Christof
Germany, Freiburg Im Breisgau
Universität Freiburg
Kolbel, Heike
Germany, Duisburg
Universität Duisburg-essen
Wirth, Brunhilde
Germany, Koln
Universität zu Köln
Kirschner, Janbernd
Germany, Freiburg Im Breisgau
Universität Freiburg
Germany, Bonn
Universitätsklinikum Bonn
Lochmüller, Hanns
Germany, Freiburg Im Breisgau
Universität Freiburg
Canada, Ottawa
Université D'ottawa, Faculté de Médecine
Spain, Barcelona
Barcelona Institute of Science and Technology Bist
Baum, Petra
Unknown Affiliation
Baumann, Matthias
Unknown Affiliation
Baumgartner, Manuela
Unknown Affiliation
Blankenburg, M. R.
Unknown Affiliation
Blaschek, Astrid
Unknown Affiliation
Cordts, Isabell
Unknown Affiliation
Denecke, Jonas
Unknown Affiliation
Deschauer, Marcus
Unknown Affiliation
Gruber-Sedlmayr, Ursula
Unknown Affiliation
von der Hagen, Maja
Unknown Affiliation
Hagenacker, Tim
Unknown Affiliation
Hahn, Andreas
Unknown Affiliation
Hartmann, Hans
Unknown Affiliation
Horber, Veronka
Unknown Affiliation
Husain, Ralf A.
Unknown Affiliation
Johannsen, Jessika
Unknown Affiliation
Kaindl, Angela M.
Unknown Affiliation
Kôlker, Stefan
Unknown Affiliation
Küpper, Hanna
Unknown Affiliation
Lingor, Paul
Unknown Affiliation
Löscher, Wolfgang N.
Unknown Affiliation
Müller-Felber, Wolfgang
Unknown Affiliation
Omran, Heymut
Unknown Affiliation
Plecko, Barbara R.
Unknown Affiliation
Saffari, Afshin
Unknown Affiliation
Schlachter, Kurt
Unknown Affiliation
Schreiber, Gudrun
Unknown Affiliation
Smitka, Martin
Unknown Affiliation
Thiele, Simone
Unknown Affiliation
Vill, Katharina
Unknown Affiliation
Walter, Maggie Christine
Unknown Affiliation
Wilichowski, Ekkehard K.G.
Unknown Affiliation
Zemlin, Michael
Unknown Affiliation
Ziegler, Andreas E.
Unknown Affiliation
Statistics
Citations: 14
Authors: 39
Affiliations: 8
Identifiers
Doi:
10.1111/ene.15331
ISSN:
13515101
Study Design
Cohort Study