% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Meyer:276085,
author = {Meyer, Thomas and Schumann, Peggy and Grehl, Torsten and
Weyen, Ute and Petri, Susanne and Rödiger, Annekathrin and
Steinbach, Robert and Grosskreutz, Julian and Bernsen, Sarah
and Weydt, Patrick and Wolf, Joachim and Günther, René and
Vidovic, Maximilian and Baum, Petra and Metelmann, Moritz
and Weishaupt, Jochen H and Streubel, Berthold and Kasper,
David C and Koc, Yasemin and Kettemann, Dagmar and Norden,
Jenny and Schmitt, Philipp and Walter, Bertram and Münch,
Christoph and Spittel, Susanne and Maier, André and
Körtvelyessy, Peter},
title = {{SOD}1 gene screening in {ALS} - frequency of mutations,
patients' attitudes to genetic information and transition to
tofersen treatment in a multi-center program.},
journal = {Amyotrophic lateral sclerosis $\&$ frontotemporal
degeneration},
volume = {26},
number = {1-2},
issn = {2167-8421},
address = {Abingdon},
publisher = {Taylor Francis Group},
reportid = {DZNE-2025-00166},
pages = {162 - 171},
year = {2025},
abstract = {To report the frequency of pathogenic SOD1 gene variants in
a screening program in amyotrophic lateral sclerosis (ALS),
and the clinical practice of transition to an expanded
access program (EAP) of tofersen treatment.From October 2021
to February 2024, at 11 ALS centers in Germany genetic
testing for SOD1, FUS, TARDBP, and C9orf72 was performed.
Patients were offered to opt for notification either about
all genetic variants or SOD1 variants relevant for tofersen
therapy. The transition to the EAP with tofersen was
assessed.1935 patients were screened $(94.7\%$ sporadic
ALS). $48.8\%$ (n = 928) opted for notification of
treatment-relevant information. Genetic variants were found
as follows: SOD1 (likely) pathogenic variants (class 4/5)
$1.8\%$ (n = 34), variants of unknown significance (class 3)
$0.8\%$ (n = 16), FUS (class 4/5) $0.9\%$ (n = 17), TARDBP
(class 4/5) $1.3\%$ (n = 25), C9orf72 hexanucleotide repeat
expansion $7.0\%$ (n = 135). In SOD1-ALS (encompassing class
3-5 variants, n = 50), $68.0\%$ (n = 34) reported a negative
family history. $74.0\%$ (n = 37) of SOD1-ALS patients -
which represent $1.9\%$ of all participants of the screening
program - were transitioned to tofersen. Median duration
from start of genetic testing to treatment was 94 days (57
to 295 days). Eight patients declined treatment whereas five
individuals died before initiation of therapy.The finding of
SOD1 variants in patients with a negative family history
underscores the need for a broad genetic screening in ALS.
In SOD1-ALS, the treatment option with tofersen was mostly
utilized. The wide range in the transition time to tofersen
calls for a SOD1-ALS management program.},
keywords = {Humans / Amyotrophic Lateral Sclerosis: genetics /
Amyotrophic Lateral Sclerosis: drug therapy / Amyotrophic
Lateral Sclerosis: diagnosis / Superoxide Dismutase-1:
genetics / Male / Female / Genetic Testing: methods / Middle
Aged / Mutation: genetics / Aged / Adult / C9orf72 Protein:
genetics / Germany / RNA-Binding Protein FUS: genetics /
DNA-Binding Proteins / Amyotrophic lateral sclerosis (Other)
/ SOD1 gene (Other) / screening (Other) / tofersen (Other) /
transition (Other) / Superoxide Dismutase-1 (NLM Chemicals)
/ SOD1 protein, human (NLM Chemicals) / C9orf72 Protein (NLM
Chemicals) / TARDBP protein, human (NLM Chemicals) / C9orf72
protein, human (NLM Chemicals) / RNA-Binding Protein FUS
(NLM Chemicals) / FUS protein, human (NLM Chemicals) /
DNA-Binding Proteins (NLM Chemicals)},
cin = {Clinical Research (Bonn) / AG Falkenburger},
ddc = {610},
cid = {I:(DE-2719)1011001 / I:(DE-2719)1710012},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39268612},
doi = {10.1080/21678421.2024.2401131},
url = {https://pub.dzne.de/record/276085},
}