Journal Article

DZNE-2023-00466

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: Treatment experience in clinical practice.

Meyer, T. ; Schumann, P. ; Weydt, P.DZNE* ; Petri, S. ; Koc, Y. ; Spittel, S. ; Bernsen, S.Extern* ; Günther, R.DZNE* ; Weishaupt, J. H. ; Dreger, M. ; Kolzarek, F. ; Kettemann, D. ; Norden, J. ; Boentert, M. ; Vidovic, M. ; Meisel, C. ; Münch, C. ; Maier, A. ; Körtvélyessy, P. (Last author)DZNE*

2023
Wiley New York, NY [u.a.]

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Please use a persistent id in citations: doi:10.1002/mus.27818

Abstract: In amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) gene mutations (SOD1-ALS), the antisense oligonucleotide tofersen had been investigated in a phase III study (VALOR) and subsequently introduced in an expanded access program. In this study we assess neurofilament light chain (NfL) before and during tofersen treatment.In six SOD1-ALS patients treated with tofersen at three specialized ALS centers in Germany, NfL in cerebrospinal fluid (CSF-NfL) and/or serum (sNfL) were investigated using the ALS Functional Rating Scale Revised (ALSFRS-R) and ALS progression rate (ALS-PR), defined by monthly decline of ALSFRS-R.Three of the six SOD1-ALS patients reported a negative family history. Three patients harbored a homozygous c.272A > C, p.(Asp91Ala) mutation. These and two other patients showed slower progressing ALS (defined by ALS-PR <0.9), whereas one patient demonstrated rapidly progressing ALS (ALS-PR = 2.66). Mean treatment duration was 6.5 (range 5 to 8) months. In all patients, NfL decreased (mean CSF-NfL: -66%, range -52% to -86%; mean sNfL: -62%, range -36% to -84%). sNfL after 5 months of tofersen treatment was significantly reduced compared with the nearest pretreatment measurement (P = .017). ALS-PR decreased in two patients, whereas no changes in ALSFRS-R were observed in four participants who had very low ALS-PR or ALSFRS-R values before treatment.In this case series, the significant NfL decline after tofersen treatment confirmed its value as response biomarker in an expanded clinical spectrum of SOD1-ALS. Given the previously reported strong correlation between sNfL and ALS progression, the NfL treatment response supports the notion of tofersen having disease-modifying activity.

Keyword(s): Humans (MeSH) ; Amyotrophic Lateral Sclerosis: drug therapy (MeSH) ; Amyotrophic Lateral Sclerosis: genetics (MeSH) ; Oligonucleotides, Antisense: therapeutic use (MeSH) ; Superoxide Dismutase-1: genetics (MeSH) ; Intermediate Filaments (MeSH) ; Biomarkers (MeSH) ; Neurofilament Proteins (MeSH) ; tofersen ; amyotrophic lateral sclerosis ; neurofilament light chain ; tofersen ; Oligonucleotides, Antisense ; Superoxide Dismutase-1 ; Biomarkers ; Neurofilament Proteins ; SOD1 protein, human

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Contributing Institute(s):

1. Clinical Research Coordination (AG Klockgether)
2. Clinical Study Team Dresden (Clinical Study Team Dresden ; AG Falkenburger)
3. Clinical Neurophysiology and Memory (AG Düzel 3)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2023

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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