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@ARTICLE{Meyer:257590,
author = {Meyer, Thomas and Schumann, Peggy and Weydt, Patrick and
Petri, Susanne and Koc, Yasemin and Spittel, Susanne and
Bernsen, Sarah and Günther, René and Weishaupt, Jochen H
and Dreger, Marie and Kolzarek, Felix and Kettemann, Dagmar
and Norden, Jenny and Boentert, Matthias and Vidovic,
Maximilian and Meisel, Christian and Münch, Christoph and
Maier, André and Körtvélyessy, Péter},
title = {{N}eurofilament light-chain response during therapy with
antisense oligonucleotide tofersen in {SOD}1-related {ALS}:
{T}reatment experience in clinical practice.},
journal = {Muscle $\&$ nerve},
volume = {67},
number = {6},
issn = {0148-639X},
address = {New York, NY [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2023-00466},
pages = {515 - 521},
year = {2023},
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.},
keywords = {Humans / Amyotrophic Lateral Sclerosis: drug therapy /
Amyotrophic Lateral Sclerosis: genetics / Oligonucleotides,
Antisense: therapeutic use / Superoxide Dismutase-1:
genetics / Intermediate Filaments / Biomarkers /
Neurofilament Proteins / tofersen (NLM Chemicals) /
amyotrophic lateral sclerosis (Other) / neurofilament light
chain (Other) / tofersen (Other) / Oligonucleotides,
Antisense (NLM Chemicals) / Superoxide Dismutase-1 (NLM
Chemicals) / Biomarkers (NLM Chemicals) / Neurofilament
Proteins (NLM Chemicals) / SOD1 protein, human (NLM
Chemicals)},
cin = {AG Klockgether / Clinical Study Team Dresden ; AG
Falkenburger / AG Düzel 3},
ddc = {610},
cid = {I:(DE-2719)1011001 / I:(DE-2719)1710012 /
I:(DE-2719)5000006},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36928619},
doi = {10.1002/mus.27818},
url = {https://pub.dzne.de/record/257590},
}