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Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: treatment experience in clinical practice: clinical research short report

Introduction/Aims 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 neu...

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Main Authors: Meyer, Thomas (Author) , Schumann, Peggy (Author) , Weydt, Patrick (Author) , Petri, Susanne (Author) , Koc, Yasemin (Author) , Spittel, Susanne (Author) , Bernsen, Sarah (Author) , Günther, René (Author) , Weishaupt, Jochen H. (Author) , Dreger, Marie (Author) , Kolzarek, Felix (Author) , Kettemann, Dagmar (Author) , Norden, Jenny (Author) , Boentert, Matthias (Author) , Vidovic, Maximilian (Author) , Meisel, Christian (Author) , Münch, Christoph (Author) , Maier, André (Author) , Körtvélyessy, Péter (Author)
Format: Article (Journal)
Language:English
Published: June 2023
In: Muscle & nerve
Year: 2023, Volume: 67, Issue: 6, Pages: 515-521
ISSN:1097-4598
DOI:10.1002/mus.27818
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/mus.27818
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/mus.27818
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Author Notes:Thomas Meyer, Peggy Schumann, Patrick Weydt, Susanne Petri, Yasemin Koc, Susanne Spittel, Sarah Bernsen, René Günther, Jochen H. Weishaupt, Marie Dreger, Felix Kolzarek, Dagmar Kettemann, Jenny Norden, Matthias Boentert, Maximilian Vidovic, Christian Meisel, Christoph Münch, André Maier, Péter Körtvélyessy
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Summary:Introduction/Aims 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. Methods 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. Results 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. Discussion 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.
Item Description:Online veröffentlicht: 16. März 2023
Gesehen am 15.07.2024
Physical Description:Online Resource
ISSN:1097-4598
DOI:10.1002/mus.27818

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