Abstract
In Part I of this Review we evaluated the scientific evidence for a Metabolic Model of multiple sclerosis (MS). Part II outlines the implementation of an adaptive pathology-supported genetic testing (PSGT) algorithm aimed at preventing/reversing disability in two illustrative MS cases, starting with a questionnaire-based risk assessment, including family history and lifestyle factors. Measurement of iron, vitamin B12, vitamin D, cholesterol and homocysteine levels identified biochemical deficits in both cases. Case 1, after following the PSGT program for 15 years, had an expanded disability status scale (EDSS) of 2.0 (no neurological sequelae) together with preserved brain volume on magnetic resonance imaging (MRI). A novel form of iron deficiency was identified in Case 1, as biochemical testing at each hospital submission due to MS symptoms showed low serum iron, ferritin and transferrin saturation, while hematological status and erythrocyte sedimentation rate measurement of systemic inflammation remained normal. Case 2 was unable to walk unaided until her EDSS improved from 6.5 to 4.0 over 12 months after implementation of the PSGT program, with amelioration of her suboptimal biochemical markers and changes to her diet and lifestyle, allowing her to regain independence. Genotype-phenotype correlation using a pathway panel of functional single nucleotide variants (SNVs) to facilitate clinical interpretation of whole exome sequencing (WES), elucidated the underlying metabolic pathways related to the biochemical deficits. A cure for MS will remain an elusive goal if separated from nutritional support required for production and maintenance of myelin, which can only be achieved by a lifelong investment in wellness.
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28 April 2021
A Correction to this paper has been published: https://doi.org/10.1007/s11011-021-00722-7
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We acknowledge Stellenbosch University, the National Health Laboratory Service (NHLS) and the MS Care Trust, Cape Town, South Africa for their support of the MS Project.
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SJVR, RVT, RTE and CJH wrote the manuscript. AEZ, PEH, FCVP, AAK and MJK revised the manuscript. MJK and SJVR designed the PSGT Method. CJH designed the specifications for MRI. CJH and MJ interpreted the MRI data. CJ did clinical and EDSS assessments. LW designed the Diet Questionnaire and reviewed the manuscript. MCK collected the biochemical and lifestyle data. KEM performed genetic testing and evaluated the results. AVP and CJVH evaluated the genetic data and reviewed the manuscript. All authors approved the final manuscript. The two last authors contributed equally in supervising the study.
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Funding: This study was funded by the National Health Laboratory Service Award Number 94139 and the South African BioDesign Initiative of the Department of Science and Innovation and the Technology Innovation Agency, South Africa (Grant number 401/01). SJ van Rensburg, C Hattingh, ME Kemp and KE Moremi were supported by Winetech, South Africa (Grant Number N07/09/203), and AVP by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council (MRC), with funds received from the Department of Science and Innovation, South Africa (Grant number S003665). The funding bodies had no role in the design of the study, collection, analysis, and interpretation of data or in writing of the manuscript.
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SJVR and MJK are listed as inventors on patent number 2010/ 00058 filed by Stellenbosch University. MJK is also a director and shareholder of Gknowmix (Pty) Ltd., a spin out company of the South African Medical Research Council. The remaining authors declared no conflict of interest. No writing assistance was utilised in the preparation of this manuscript.
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van Rensburg, S.J., Hattingh, C., Johannes, C. et al. Pathology-supported genetic testing as a method for disability prevention in multiple sclerosis (MS). Part II. Insights from two MS cases. Metab Brain Dis 36, 1169–1181 (2021). https://doi.org/10.1007/s11011-021-00712-9
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DOI: https://doi.org/10.1007/s11011-021-00712-9