Neurofilament light-chain response during therapy with antisense oligonucleotide tofersen in SOD1-related ALS: Treatment experience in clinical practice

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Thomas Meyer - , Charité – Universitätsmedizin Berlin, Ambulanzpartner Soziotechnologie APST GmbH (Autor:in)
  • Peggy Schumann - , Ambulanzpartner Soziotechnologie APST GmbH (Autor:in)
  • Patrick Weydt - , Universitätsklinikum Bonn (Autor:in)
  • Susanne Petri - , Medizinische Hochschule Hannover (MHH) (Autor:in)
  • Yasemin Koc - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Susanne Spittel - , Ambulanzpartner Soziotechnologie APST GmbH (Autor:in)
  • Sarah Bernsen - , Charité – Universitätsmedizin Berlin (Autor:in)
  • René Günther - , Klinik und Poliklinik für Neurologie, Deutsches Zentrum für Neurodegenerative Erkrankungen, Standort Dresden (Partner: DZNE der Helmholtzgemeinschaft) (Autor:in)
  • Jochen H Weishaupt - , Nationales Zentrum für Tumorerkrankungen (NCT) Heidelberg (Autor:in)
  • Marie Dreger - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Felix Kolzarek - , Ambulanzpartner Soziotechnologie APST GmbH (Autor:in)
  • Dagmar Kettemann - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Jenny Norden - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Matthias Boentert - , Universitätsklinikum Münster (Autor:in)
  • Maximilian Vidovic - , Klinik und Poliklinik für Neurologie (Autor:in)
  • Christian Meisel - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Christoph Münch - , Charité – Universitätsmedizin Berlin (Autor:in)
  • André Maier - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Péter Körtvélyessy - , Charité – Universitätsmedizin Berlin (Autor:in)

Abstract

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)515-521
Seitenumfang7
Fachzeitschrift Muscle & nerve : official journal of the American Association of Electrodiagnostic Medicine
Jahrgang67
Ausgabenummer6
PublikationsstatusVeröffentlicht - Juni 2023
Peer-Review-StatusJa

Externe IDs

Scopus 85151922108

Schlagworte

Schlagwörter

  • Amyotrophic Lateral Sclerosis/drug therapy, Biomarkers, Humans, Intermediate Filaments, Neurofilament Proteins, Oligonucleotides, Antisense/therapeutic use, Superoxide Dismutase-1/genetics