Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Department of Pediatric Medicine and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Metab Brain Dis. 2021 Aug;36(6):1151-1167. doi: 10.1007/s11011-021-00711-w. Epub 2021 Apr 28.
In this Review (Part I), we investigate the scientific evidence that multiple sclerosis (MS) is caused by the death of oligodendrocytes, the cells that synthesize myelin, due to a lack of biochemical and nutritional factors involved in mitochondrial energy production in these cells. In MS, damage to the myelin sheaths surrounding nerve axons causes disruption of signal transmission from the brain to peripheral organs, which may lead to disability. However, the extent of disability is not deterred by the use of MS medication, which is based on the autoimmune hypothesis of MS. Rather, disability is associated with the loss of brain volume, which is related to the loss of grey and white matter. A pathology-supported genetic testing (PSGT) method, developed for personalized assessment and treatment to prevent brain volume loss and disability progression in MS is discussed. This involves identification of MS-related pathogenic pathways underpinned by genetic variation and lifestyle risk factors that may converge into biochemical abnormalities associated with adverse expanded disability status scale (EDSS) outcomes and magnetic resonance imaging (MRI) findings during patient follow-up. A Metabolic Model is presented which hypothesizes that disability may be prevented or reversed when oligodendrocytes are protected by nutritional reserve. Evidence for the validity of the Metabolic Model may be evaluated in consecutive test cases following the PSGT method. In Part II of this Review, two cases are presented that describe the PSGT procedures and the clinical outcomes of these individuals diagnosed with MS.
在这篇综述（第一部分）中，我们调查了多发性硬化症（MS）是由少突胶质细胞（合成髓鞘的细胞）死亡引起的科学证据，这种死亡是由于这些细胞中线粒体能量产生所涉及的生化和营养因素的缺乏。在多发性硬化症中，神经轴突周围的髓鞘护套受损会导致大脑向周围器官传递信号的中断，这可能导致残疾。然而，残疾的程度并没有因多发性硬化症药物的使用而受到抑制，这些药物是基于多发性硬化症的自身免疫假说。相反，残疾与脑容量的丧失有关，而脑容量的丧失与灰质和白质的丧失有关。本文讨论了一种基于病理支持的遗传检测（PSGT）方法，该方法用于个性化评估和治疗，以防止多发性硬化症患者的脑容量损失和残疾进展。这涉及到识别由遗传变异和生活方式风险因素支持的多发性硬化症相关致病途径，这些途径可能会导致与不良扩展残疾状况量表（EDSS）结果和磁共振成像（MRI）发现相关的生化异常，这些异常在患者随访期间会出现。提出了一种代谢模型，该模型假设当少突胶质细胞受到营养储备的保护时，残疾可能会被预防或逆转。可以通过遵循 PSGT 方法，在连续的测试案例中评估代谢模型的有效性。在这篇综述的第二部分，介绍了两个病例，描述了 PSGT 程序和这些被诊断为多发性硬化症的个体的临床结果。
