FGF23, a novel muscle biomarker detected in the early stages of ALS
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle weakness. Currently, there are no biomarkers that can predict prognosis or disease progression. FGF23 is a protein secreted in the plasma by bone cells. A recent report identifies skeletal muscle as a potential target of FGF23. In a large collection of human ALS muscle samples the researchers observed that FGF23 protein is increased up to 50-fold in ALS muscle tissues .This report raises important questions of the role of FGF23 in ALS disease pathology.
Learn more: FGF23, a novel muscle biomarker detected in the early stages of ALS. Si Y, Kazamel M, Benatar M, Wuu J, Kwon Y, Kwan T, Jiang N, Kentrup D, Faul C, Alesce L, King PH. Sci Rep. 2021 Jun 8;11(1):12062. doi: 10.1038/s41598-021-91496-6. PMID: 34103575; PMCID: PMC8187665.
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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.
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The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS). Boddy SL, Giovannelli I, Sassani M, Cooper-Knock J, Snyder MP, Segal E, Elinav E, Barker LA, Shaw PJ, McDermott CJ. BMC Med. 2021 Jan 20;19(1):13. doi: 10.1186/s12916-020-01885-3. PMID: 33468103; PMCID: PMC7816375. Full text link
Gene therapy for ALS: A review. Amado DA, Davidson BL. Mol Ther. 2021 Apr 9:S1525-0016(21)00195-7. doi: 10.1016/j.ymthe.2021.04.008. Epub ahead of print. PMID: 33839324. Full text link
Total Neuropilin-1 ELISA (cat.no. BI-20409)
Expression of the axon-guidance protein receptor Neuropilin 1 is increased in the spinal cord and decreased in muscle of a mouse model of amyotrophic lateral sclerosis. Körner S et al., Eur J Neurosci. 2019.