FGF23, a novel muscle biomarker detected in the early stages of ALS

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we ident...

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Autores principales:	Ying Si, Mohamed Kazamel, Michael Benatar, Joanne Wuu, Yuri Kwon, Thaddaeus Kwan, Nan Jiang, Dominik Kentrup, Christian Faul, Lyndsy Alesce, Peter H. King
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f8008a5ad874d87a61a78f2f91ba8e9
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spelling	oai:doaj.org-article:0f8008a5ad874d87a61a78f2f91ba8e92021-12-02T14:59:29ZFGF23, a novel muscle biomarker detected in the early stages of ALS10.1038/s41598-021-91496-62045-2322https://doaj.org/article/0f8008a5ad874d87a61a78f2f91ba8e92021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91496-6https://doaj.org/toc/2045-2322Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.Ying SiMohamed KazamelMichael BenatarJoanne WuuYuri KwonThaddaeus KwanNan JiangDominik KentrupChristian FaulLyndsy AlescePeter H. KingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ying Si Mohamed Kazamel Michael Benatar Joanne Wuu Yuri Kwon Thaddaeus Kwan Nan Jiang Dominik Kentrup Christian Faul Lyndsy Alesce Peter H. King FGF23, a novel muscle biomarker detected in the early stages of ALS
description	Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Skeletal muscle is a prime source for biomarker discovery since it is one of the earliest sites to manifest disease pathology. From a prior RNA sequencing project, we identified FGF23 as a potential muscle biomarker in ALS. Here, we validate this finding with a large collection of ALS muscle samples and found a 13-fold increase over normal controls. FGF23 was also increased in the SOD1G93A mouse, beginning at a very early stage and well before the onset of clinical symptoms. FGF23 levels progressively increased through end-stage in the mouse. Immunohistochemistry of ALS muscle showed prominent FGF23 immunoreactivity in the endomysial connective tissue and along the muscle membrane and was significantly higher around grouped atrophic fibers compared to non-atrophic fibers. ELISA of plasma samples from the SOD1G93A mouse showed an increase in FGF23 at end-stage whereas no increase was detected in a large cohort of ALS patients. In conclusion, FGF23 is a novel muscle biomarker in ALS and joins a molecular signature that emerges in very early preclinical stages. The early appearance of FGF23 and its progressive increase with disease progression offers a new direction for exploring the molecular basis and response to the underlying pathology of ALS.
format	article
author	Ying Si Mohamed Kazamel Michael Benatar Joanne Wuu Yuri Kwon Thaddaeus Kwan Nan Jiang Dominik Kentrup Christian Faul Lyndsy Alesce Peter H. King
author_facet	Ying Si Mohamed Kazamel Michael Benatar Joanne Wuu Yuri Kwon Thaddaeus Kwan Nan Jiang Dominik Kentrup Christian Faul Lyndsy Alesce Peter H. King
author_sort	Ying Si
title	FGF23, a novel muscle biomarker detected in the early stages of ALS
title_short	FGF23, a novel muscle biomarker detected in the early stages of ALS
title_full	FGF23, a novel muscle biomarker detected in the early stages of ALS
title_fullStr	FGF23, a novel muscle biomarker detected in the early stages of ALS
title_full_unstemmed	FGF23, a novel muscle biomarker detected in the early stages of ALS
title_sort	fgf23, a novel muscle biomarker detected in the early stages of als
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0f8008a5ad874d87a61a78f2f91ba8e9
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FGF23, a novel muscle biomarker detected in the early stages of ALS

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