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@ARTICLE{Bernsen:280914,
author = {Bernsen, Sarah and Fabian, Rachel and Koc, Yasemin and
Schumann, Peggy and Körtvélyessy, Peter and Castro-Gomez,
Mario Sergio and Meyer, Thomas and Weydt, Patrick},
title = {{S}erum {C}ardiac {T}roponin {T} {L}evels as a {T}herapy
{R}esponse {M}arker in {T}ofersen-{T}reated {ALS}.},
journal = {Muscle $\&$ nerve},
volume = {72},
number = {3},
issn = {0148-639X},
address = {New York, NY [u.a.]},
publisher = {Wiley},
reportid = {DZNE-2025-00997},
pages = {509 - 514},
year = {2025},
abstract = {Cardiac troponin T (cTnT) levels are elevated in the
majority of persons with amyotrophic lateral sclerosis (ALS)
and increase over time. Neurofilament light chain (NfL) is
an established therapy response biomarker in ALS as
superoxide dismutase1 (SOD1)-ALS patients treated with the
antisense oligonucleotide tofersen show a decrease in NfL.
In this study, we assess cTnT levels in SOD1-ALS at baseline
and during tofersen treatment.cTnT was analyzed at baseline
and during tofersen treatment in 23 SOD1-ALS patients at two
specialized ALS centers in Germany and compared to a control
cohort of 74 ALS patients without SOD1 variants.cTnT levels
increased in the control ALS cohort over time (p < 0.0001)
but not in the tofersen group (p = 0.36). Creatine kinase
(CK) and CK-MB levels did not show significant changes over
time. The median monthly increase of cTnT was 0.045 points
(IQR 0.02-0.08) in the control ALS cohort and 0.01 points
(IQR -0.01-0.03) in the tofersen group (p = 0.0013). A
significantly lower fold change in cTnT levels was observed
in the tofersen-treated cohort (median 1.2; IQR 0.77-1.59)
relative to the control group (median 1.89; IQR 1.35-2.75)
(p = 0.0003). Nine $(39\%)$ patients treated with tofersen
experienced a reduction in cTnT levels.In this study, we
describe a response signal of cTnT to tofersen treatment,
which supports the value of cTnT as an independent biomarker
in ALS. These results contribute to the notion that cTnT may
provide additional value as a progression and treatment
response biomarker in ALS complementary to NfL and warrant
further investigation.},
keywords = {Humans / Amyotrophic Lateral Sclerosis: blood / Amyotrophic
Lateral Sclerosis: drug therapy / Amyotrophic Lateral
Sclerosis: genetics / Troponin T: blood / Male / Female /
Middle Aged / Aged / Biomarkers: blood / Oligonucleotides:
therapeutic use / Treatment Outcome / Neurofilament Proteins
/ Superoxide Dismutase-1: genetics / Cohort Studies / Adult
/ Creatine Kinase: blood / SOD1 (Other) / amyotrophic
lateral sclerosis (Other) / biomarker (Other) / tofersen
(Other) / troponin (Other) / Troponin T (NLM Chemicals) /
Biomarkers (NLM Chemicals) / Oligonucleotides (NLM
Chemicals) / Neurofilament Proteins (NLM Chemicals) /
Superoxide Dismutase-1 (NLM Chemicals) / Creatine Kinase
(NLM Chemicals) / neurofilament protein L (NLM Chemicals)},
cin = {Clinical Research (Bonn) / AG Radbruch / AG Düzel},
ddc = {610},
cid = {I:(DE-2719)1011001 / I:(DE-2719)5000075 /
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:40491248},
pmc = {pmc:PMC12338008},
doi = {10.1002/mus.28453},
url = {https://pub.dzne.de/record/280914},
}