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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1482999

Serum Metabolomic Signatures of Patients with Rare Neurogenetic Diseases: An Insight into Potential Biomarkers and Treatment Targets

Provisionally accepted
Nalaka Wijekoon Nalaka Wijekoon 1,2Lakmal Gonawala Lakmal Gonawala 1,3Pyara Ratnayake Pyara Ratnayake 4Darshana Sirisena Darshana Sirisena 5Harsha Gunasekara Harsha Gunasekara 6Athula Dissanayake Athula Dissanayake 7Dhammika Amaratunga Dhammika Amaratunga 8Harry Wilhelm Steinbusch Harry Wilhelm Steinbusch 3Yetrib Hathoiut Yetrib Hathoiut 9Eric P Hoffman Eric P Hoffman 9Ashwin Dalal Ashwin Dalal 10Chandra Mohan Chandra Mohan 11Ranil De Silva Ranil De Silva 1*
  • 1 University of Sri Jayewardenepura, Nugegoda, Sri Lanka
  • 2 School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands, Netherlands
  • 3 Department of Neuroscience, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands, Netherlands
  • 4 Lady Ridgeway Childrens Hospital, Colombo, Sri Lanka
  • 5 Colombo North Teaching Hospital, Ragama, Sri Lanka
  • 6 Sri Jayewardenepura Hospital, Colombo, Sri Lanka
  • 7 Karapitiya Teaching Hospital, Galle, Sri Lanka
  • 8 Princeton Data Analytics, Princeton, United States
  • 9 School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Binghamton, New York, United States
  • 10 Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad, Andhra Pradesh, India
  • 11 University of Houston, Houston, Texas, United States

The final, formatted version of the article will be published soon.

    To further advance our understanding of Muscular Dystrophies (MDs) and Spinocerebellar Ataxias (SCAs), it is necessary to identify the biological patterns associated with disease pathology. Although progress has been made in the fields of genetics and transcriptomics, there is a need for proteomics and metabolomics studies. The present study aimed to be the first to document serum metabolic signatures of MDs (DMD, BMD, and LGMD 2A) SCAs (SCA 1-3), from a South Asian perspective. A total of 28 patients (SCA 1-10, SCA 2-2, SCA 3-2, DMD-10, BMD-2, LGMD-2) and eight controls (aged 8-65 years) were included. Metabolomic analysis was performed by Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS), with support from the Houston Omics Collaborative. Amino acid metabolism was the primary altered super pathway in DMD followed by carbohydrate metabolism and lipid metabolism. In contrast, BMD and LGMD 2A exhibited a more prominent alteration in lipid metabolism followed by amino acid metabolism. In SCAs, primarily lipid, amino acid, peptide, nucleotide, and xenobiotics pathways are affected. Our findings offer new insights into the variance of metabolite levels in MD and SCA, with substantial implications for pathology, drug development, therapeutic targets and clinical management. Intriguingly, this study identified two novel metabolites associated with SCA. This pilot cross-sectional study warrants further research involving larger groups of participants, to validate our findings.

    Keywords: muscular dystrophy, Ataxia, biomarker, DMD, LGMD, SCA, pathways

    Received: 19 Aug 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Wijekoon, Gonawala, Ratnayake, Sirisena, Gunasekara, Dissanayake, Amaratunga, Steinbusch, Hathoiut, Hoffman, Dalal, Mohan and De Silva. 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) or licensor 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.

    * Correspondence: Ranil De Silva, University of Sri Jayewardenepura, Nugegoda, 10250, Sri Lanka

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.