Phosphorylated neurofilament heavy chain: a potential diagnostic biomarker in amyotrophic lateral sclerosis

Heckler, Ilana; Venkataraman, Iswariya

doi:10.1152/jn.00398.2021

Cited by 9 publications

(5 citation statements)

References 59 publications

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“…This striking contrast underscores that serum cTnT captures an aspect of ALS that is missed by neurofilament levels (either in serum or in cerebrospinal fluid). It is well established that neurofilament levels reflect neuroaxonal damage 31,32 . The published information on the origin of serum cTnT levels in ALS is more circumstantial, but evidence from neuromuscular diseases supports that striated muscle expresses cTnT under pathological conditions 8 .…”

Section: Resultsmentioning

confidence: 99%

Cardiac Troponin T is a Serum Biomarker of Respiratory Dysfunction in Amyotrophic Lateral Sclerosis

Koch,

Fabian,

Weinhold

et al. 2024

Preprint

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ObjectiveInformative biomarkers are an urgent need in management and therapy development of amyotrophic lateral sclerosis. Serum cardiac troponin T is elevated in most amyotrophic lateral sclerosis patients and not correlated with neurofilaments. We sought to delineate the functional implications and the informative value of serum troponin T with regard to respiratory function, a major prognostic factor in amyotrophic lateral sclerosis.MethodsWe analyzed two independent hospital-based amyotrophic lateral sclerosis cohorts (d=discovery cohort; v= validation cohort) with data available on serum cardiac troponin T levels (nd=297; nv=49), serum neurofilament light chain levels (nd=116; nv=17), and routine respiratory test results (nd=86; nv=49).ResultsSerum cardiac troponin T levels, unlike serum neurofilaments, were strongly associated with the respiratory domain of the revised amyotrophic lateral sclerosis functional rating score (rd= - 0.29, pd= 0.001; rv= - 0.48, pv= 0.007) and with relevant pulmonary function parameters (nd), namely SVC% (r = - 0.45; p = 0.001), FVC% (r = - 0.43; p = 0.001), FEV1% (r = −0.37, p = 0.007), and PEF (r = - 0.34, p = 0.027).Serum cardiac Troponin T reliably discriminated benchmarks of SVC% < 80%: (AUC 0.75, p = 0.003), FVC % < 80%: (AUC 0.72, p = 0.011) and PEF% <75%: (AUC 0.72, p = 0.015).InterpretationOur findings confirm cardiac Troponin T as an informative serum biomarker in amyotrophic lateral sclerosis, complementing neurofilaments. Serum Troponin T can flag compromised respiratory function in amyotrophic lateral sclerosis and might prove useful as a proxy of respiratory impairment with prognostic implications.

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Section: Resultsmentioning

confidence: 99%

Cardiac Troponin T is a Serum Biomarker of Respiratory Dysfunction in Amyotrophic Lateral Sclerosis

Koch,

Fabian,

Weinhold

et al. 2024

Preprint

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“…In addition, administration of BIIB067 to transgenic hSOD1 G93A rodents prior to disease onset significantly prolonged survival, slowed motor impairment, and reduced neuromuscular damage [19]. ASO therapy also reduced serum levels of phosphorylated neurofilament heavy chain (pNFH) [19], a cytoskeletal protein released in cerebrospinal fluid during axonal injury and correlated with disease severity [69]. When administered after disease onset, ASOs suppressed further increases in pNFH and restored neuromuscular activity close to baseline.…”

Section: Sod1 Genementioning

confidence: 98%

Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade

Cantara,

Simoncelli,

Ricci

2024

IJMS

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Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins, and decrease levels of toxic proteins. ASOs are being developed for the treatment of motor neuron diseases (MNDs), including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MNDs, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

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“…In addition, administration of BIIB067 to transgenic hSOD1 G93A rodents prior to disease onset significantly prolonged survival, slowed motor impairment and reduced neuromuscular damage [19]. ASO therapy also reduced serum levels of phosphorylated neurofilament heavy chain (pNFH) [19], a cytoskeletal protein released in cerebrospinal fluid during axonal injury and correlated with disease severity [68]. When administered after disease onset, ASOs suppressed further increases in pNFH and restored neuromuscular activity close to baseline.…”

Section: Sod1 Genementioning

confidence: 99%

Antisense oligonucleotides (ASOs) in motor neuron diseases: a road to cure in light and shade

Cantara,

Simoncelli,

Ricci

2024

Preprint

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Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins and decrease levels of toxic proteins. ASOs are being developed for the treatment of several diseases, including motor neuron diseases (MNDs), a group of neurodegenerative disorders characterised by the loss of motor neurons, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MND, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

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Phosphorylated neurofilament heavy chain: a potential diagnostic biomarker in amyotrophic lateral sclerosis

Cited by 9 publications

References 59 publications

Cardiac Troponin T is a Serum Biomarker of Respiratory Dysfunction in Amyotrophic Lateral Sclerosis

Cardiac Troponin T is a Serum Biomarker of Respiratory Dysfunction in Amyotrophic Lateral Sclerosis

Antisense Oligonucleotides (ASOs) in Motor Neuron Diseases: A Road to Cure in Light and Shade

Antisense oligonucleotides (ASOs) in motor neuron diseases: a road to cure in light and shade

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