Searching for just a few words should be enough to get started. If you need to make more complex queries, use the tips below to guide you.
Article type: Research Article
Authors: Rich, Kelly A.a | Fox, Ashleya | Yalvac, Mehmeta | Heintzman, Saraha | Tellez, Marcoa | Bartlett, Amya | Severyn, Stevenb | Linsenmayer, Mathewc | Kelly, Kristinaa | Reynolds, Jerrya | Sterling, Gary Brenta | Weaver, Tristanb | Rajneesh, Kirana | Pino, Megan G.a | Arnold, W. Davida | Elsheikh, Bakria | Kolb, Stephen J.a; d; *
Affiliations: [a] Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, OH, USA | [b] Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA | [c] Assistive Technology Department, The Ohio State University Wexner Medical Center, Columbus, OH, USA | [d] Department of Biological Chemistry & Pharmacology, The Ohio State University, Columbus, OH, USA
Correspondence: [*] Correspondence to: Stephen J. Kolb, MD, PhD (SJK), Rightmire Hall, Rm 226A, 1060 Carmack Road, Columbus, OH 43210, USA. Tel.: +1 614 292 3545; Fax: +1 614 292 4118; E-mail: stephen.kolb@osumc.edu.
Abstract: Objective:To retrospectively evaluate the utility of serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH) as biomarkers for spinal muscular atrophy (SMA) progression and response to nusinersen treatment. Methods:NfL and pNfH levels were quantified using single molecular array (SIMOA) in CSF of 33 adult SMA patients (SMN copy number 3–5) before and in response to nusinersen treatment. In 11 of the patients, blood serum samples were also collected. CSF NfL and pNfH from patients were compared to CSF Nfs from age-matched controls without neurological disease (n = 6). For patients, pearson correlation coefficients (r) were calculated to investigate associations between Nf levels and other functional outcome measures. Results:Nf levels were similar between SMA and control adults and showed no change in response to nusinersen treatment in CSF or serum. Cross-sectional analyses showed an increase in CSF NfL and pNfH with age in patients (NfL p = 0.0013; pNfH p = 0.0035) and an increase in CSF NfL in controls (p = 0.002). In non-ambulatory patients, baseline serum pNfH showed a negative correlation with multiple strength and functional assessment metrics including Revised Upper Limb Module (r = –0.822, p = 0.04), upper extremity strength (r = –0.828, p = 0.042), lower extremity strength (r = –0.860, p = 0.028), and total strength (r = –0.870, p = 0.024). Conclusions:Nf levels did not change in response to nusinersen in adults with SMA and were not different from controls. In patients and controls, we detected an age-related increase in baseline CSF NfL and pNfH levels. Though some associations were identified, our results suggest Nf levels are not preditive or prognostic biomarkers in this population.
Keywords: Adult spinal muscular atrophy, neurofilament protein, biomarker, aging
DOI: 10.3233/JND-210735
Journal: Journal of Neuromuscular Diseases, vol. 9, no. 1, pp. 111-119, 2022
IOS Press, Inc.
6751 Tepper Drive
Clifton, VA 20124
USA
Tel: +1 703 830 6300
Fax: +1 703 830 2300
sales@iospress.com
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
IOS Press
Nieuwe Hemweg 6B
1013 BG Amsterdam
The Netherlands
Tel: +31 20 688 3355
Fax: +31 20 687 0091
info@iospress.nl
For editorial issues, permissions, book requests, submissions and proceedings, contact the Amsterdam office info@iospress.nl
Inspirees International (China Office)
Ciyunsi Beili 207(CapitaLand), Bld 1, 7-901
100025, Beijing
China
Free service line: 400 661 8717
Fax: +86 10 8446 7947
china@iospress.cn
For editorial issues, like the status of your submitted paper or proposals, write to editorial@iospress.nl
如果您在出版方面需要帮助或有任何建, 件至: editorial@iospress.nl