Jaervilehto, Julius;
Harjuhaahto, Sandra;
Palu, Edouard;
Auranen, Mari;
Kvist, Jouni;
Zetterberg, Henrik;
Koskivuori, Johanna;
... Tyynismaa, Henna; + view all
(2022)
Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy.
Frontiers in Neurology
, 13
, Article 793937. 10.3389/fneur.2022.793937.
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Abstract
Objective: To characterize serum biomarkers in mitochondrial CHCHD10-linked spinal muscular atrophy Jokela (SMAJ) type for disease monitoring and for the understanding of pathogenic mechanisms. Methods: We collected serum samples from a cohort of 49 patients with SMAJ, all carriers of the heterozygous c.197G>T p.G66V variant in CHCHD10. As controls, we used age- and sex-matched serum samples obtained from Helsinki Biobank. Creatine kinase and creatinine were measured by standard methods. Neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured with single molecule array (Simoa), fibroblast growth factor 21 (FGF-21), and growth differentiation factor 15 (GDF-15) with an enzyme-linked immunosorbent assay. For non-targeted plasma metabolite profiling, samples were analyzed with liquid chromatography high-resolution mass spectrometry. Disease severity was evaluated retrospectively by calculating a symptom-based score. Results: Axon degeneration marker, NfL, was unexpectedly not altered in the serum of patients with SMAJ, whereas astrocytic activation marker, GFAP, was slightly decreased. Creatine kinase was elevated in most patients, particularly men. We identified six metabolites that were significantly altered in serum of patients with SMAJ in comparison to controls: increased creatine and pyruvate, and decreased creatinine, taurine, N-acetyl-carnosine, and succinate. Creatine correlated with disease severity. Altered pyruvate and succinate indicated a metabolic response to mitochondrial dysfunction; however, lactate or mitochondrial myopathy markers FGF-21 or GDF-15 was not changed. Conclusions: Biomarkers of muscle mass and damage are altered in SMAJ serum, indicating a role for skeletal muscle in disease pathogenesis in addition to neurogenic damage. Despite the minimal mitochondrial pathology in skeletal muscle, signs of a metabolic shift can be detected.
Type: | Article |
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Title: | Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy |
Location: | Switzerland |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.3389/fneur.2022.793937 |
Publisher version: | https://doi.org/10.3389/fneur.2022.793937 |
Language: | English |
Additional information: | © 2022 Järvilehto, Harjuhaahto, Palu, Auranen, Kvist, Zetterberg, Koskivuori, Lehtonen, Saukkonen, Jokela, Ylikallio and Tyynismaa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: | Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences, Neurosciences & Neurology, biomarker, NEFL, CHCHD10, SMAJ, creatine, MOTOR NEURONOPATHY, BIOMARKER, CHAIN, DISEASE |
UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10146081 |
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