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The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy
OBJECTIVES: To investigate the levels of neurofilaments (NFs) in transgenic mice and patients with spinal muscular atrophy (SMA), and to evaluate their efficacy as a biomarker in SMA. METHODS: The levels of NF mRNA transcripts were measured by quantitative real‐time PCR in spinal cord from SMA mice....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045929/ https://www.ncbi.nlm.nih.gov/pubmed/33683023 http://dx.doi.org/10.1002/acn3.51336 |
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author | Spicer, Charlotte Lu, Ching‐Hua Catapano, Francesco Scoto, Mariacristina Zaharieva, Irina Malaspina, Andrea Morgan, Jennifer E. Greensmith, Linda Muntoni, Francesco Zhou, Haiyan |
author_facet | Spicer, Charlotte Lu, Ching‐Hua Catapano, Francesco Scoto, Mariacristina Zaharieva, Irina Malaspina, Andrea Morgan, Jennifer E. Greensmith, Linda Muntoni, Francesco Zhou, Haiyan |
author_sort | Spicer, Charlotte |
collection | PubMed |
description | OBJECTIVES: To investigate the levels of neurofilaments (NFs) in transgenic mice and patients with spinal muscular atrophy (SMA), and to evaluate their efficacy as a biomarker in SMA. METHODS: The levels of NF mRNA transcripts were measured by quantitative real‐time PCR in spinal cord from SMA mice. Blood levels of NF heavy chain (NfH) from mice and patients were measured by an in‐house ELISA method. The response of NFs to therapeutic intervention was analysed in severe SMA mice treated with morpholino antisense oligonucleotides. RESULTS: Significant changes in NF transcript and protein in spinal cord and protein levels in blood were detected in SMA mice with severe or mild phenotypes, at different time points. A decrease in blood levels of NfH after antisense oligonucleotide treatment was only transient in the mice, despite the persistent benefit on the disease phenotype. A drastic reduction of over 90% in blood levels of NfF was observed in both control and SMA mice during early postnatal development. In contrast, blood levels of NfH were found to be decreased in older SMA children with chronic disease progression. INTERPRETATION: Our results show that blood NfH levels are informative in indicating disease onset and response to antisense oligonucleotides treatment in SMA mice, and indicate their potential as a peripheral marker reflecting the pathological status in central nervous system. In older patients with chronic SMA, however, the lower NfH levels may limit their application as biomarker, highlighting the need to continue to pursue additional biomarkers for this group of patients. |
format | Online Article Text |
id | pubmed-8045929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80459292021-04-16 The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy Spicer, Charlotte Lu, Ching‐Hua Catapano, Francesco Scoto, Mariacristina Zaharieva, Irina Malaspina, Andrea Morgan, Jennifer E. Greensmith, Linda Muntoni, Francesco Zhou, Haiyan Ann Clin Transl Neurol Research Articles OBJECTIVES: To investigate the levels of neurofilaments (NFs) in transgenic mice and patients with spinal muscular atrophy (SMA), and to evaluate their efficacy as a biomarker in SMA. METHODS: The levels of NF mRNA transcripts were measured by quantitative real‐time PCR in spinal cord from SMA mice. Blood levels of NF heavy chain (NfH) from mice and patients were measured by an in‐house ELISA method. The response of NFs to therapeutic intervention was analysed in severe SMA mice treated with morpholino antisense oligonucleotides. RESULTS: Significant changes in NF transcript and protein in spinal cord and protein levels in blood were detected in SMA mice with severe or mild phenotypes, at different time points. A decrease in blood levels of NfH after antisense oligonucleotide treatment was only transient in the mice, despite the persistent benefit on the disease phenotype. A drastic reduction of over 90% in blood levels of NfF was observed in both control and SMA mice during early postnatal development. In contrast, blood levels of NfH were found to be decreased in older SMA children with chronic disease progression. INTERPRETATION: Our results show that blood NfH levels are informative in indicating disease onset and response to antisense oligonucleotides treatment in SMA mice, and indicate their potential as a peripheral marker reflecting the pathological status in central nervous system. In older patients with chronic SMA, however, the lower NfH levels may limit their application as biomarker, highlighting the need to continue to pursue additional biomarkers for this group of patients. John Wiley and Sons Inc. 2021-03-08 /pmc/articles/PMC8045929/ /pubmed/33683023 http://dx.doi.org/10.1002/acn3.51336 Text en © 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Spicer, Charlotte Lu, Ching‐Hua Catapano, Francesco Scoto, Mariacristina Zaharieva, Irina Malaspina, Andrea Morgan, Jennifer E. Greensmith, Linda Muntoni, Francesco Zhou, Haiyan The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy |
title | The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy |
title_full | The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy |
title_fullStr | The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy |
title_full_unstemmed | The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy |
title_short | The altered expression of neurofilament in mouse models and patients with spinal muscular atrophy |
title_sort | altered expression of neurofilament in mouse models and patients with spinal muscular atrophy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045929/ https://www.ncbi.nlm.nih.gov/pubmed/33683023 http://dx.doi.org/10.1002/acn3.51336 |
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