Personalized and Precision Medicine Journal

Abstract Multiple sclerosis (MS) is a long‐term disease that is frequently progressive and affects the central nervous system (CNS). This in turn breaks down the myelin sheath the protective covering around nerve fibers. Damage to myelin leads to a breakdown in nerve communication and can cause a number of neurological conditions. This study examines recent approaches towards increasing remyelination in the multiple sclerosis (MS) population as the protection of oligodendrocytes and promotion of remyelination are essential therapeutic goals. Materials and methods: A search was performed in national and international databases with the use of specific keywords. This search resulted in the identification of 235 articles, on “remyelination” and “multiple sclerosis”. Seventy articles were included in this review from 2000 up to 2020. These findings lead to the conclusion that already established immunomodulatory therapies have some benefits for reduction of myelin breakdown, but are rather poor at promoting remyelination, most notably in progressive MS.Controversially during the last years a change has been made towards compounds targeting (symptomatic) inflammation as well as remyelination. These interventions may optimize function and may promote axonal conduction. These strategies, including stem cell therapy, growth factors, small molecules and gene therapies hold promise in future treatment of MS. Not only are they trying to stop further loss of myelin, but also attempt to repair what damage has already been done.

Abstract Multiple sclerosis (MS), the most common inflammatory demyelinating illness of the central nervous system (CNS), presents a range of clinical symptoms. The body’s immune system attacking myelin causes the transmission block in MS, which increases the electrical capacity of axons. Studies suggest that epigenetic factors play a part in the development of MS. Longer than 200 nucleotides in length and widely distributed, lncRNAs are linear RNA transcripts that cannot code for proteins. For instance, evidence suggests that lncRNAs are essential for a number of cellular functions, including immune response regulation, epithelial mesenchymal transition (EMT), cancer cell proliferation and metastasis, cellular homeostasis, and embryonic development. Epigenetic mechanisms have been proven to have a significant impact on the pathophysiology of MS, and their participation has revealed the function of lncRNAs as epigenetic regulatory molecules in molecular processes. The major subjects of this study have been the relationship between lncRNAs and MS, the role of lncRNA in the pathophysiology of the disease, and the diagnostic and prognostic potential of lncRNA in MS.

Abstract Due to the lack of reliable biomarkers and a thorough understanding of the etiology of multiple sclerosis (MS), the treatment strategy in MS requires a personalized medicine framework that goes beyond the precision medicine idea. A patient-centered approach is necessary for personalized treatment, and the identification of pathophysiological processes should be employed to help classify diseases. Intracellular aspartic proteinase-A enzyme is expressed by the APR1 gene and is one of the important factors in the development of systemic candidiasis caused by Candida albicans. The aim of this study was molecular detection of fungal DNA in serum of MS patients and to evaluate the expression of the APR1 gene in C. Albicans isolates obtained from patients with multiple sclerosis (MS) and controls. The samples were obtained from 100 MS patients with candidiasis and 100 matched controls of healthy individuals during 2018 - 2019. The evaluation of APR1 gene expression was performed using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. There was a statistically significant difference in APR1 gene expression of C. Albicans strains between MS patients (mean± SD: 0.5008 ± 0.09518) and the control group (mean± SD: 0.7513±0.10505) (P = 0.000). The mean values of EDSS were 1.4074 ± 0.0082 after antifungal treatment and 2.0519 ± 0.1123 before antifungal treatment (P = 0.000). Differences in active fungal infection between patients and controls indicate the importance and possible role of fungi in MS patients. The results suggested that APR1 gene expression in C. Albicans strains isolated from MS patients may be an important factor for invasive C. Albicans strains in the progression of MS disease. Because fungal infections in the serum causes more activity of the body’s immune and defense system and directly affect the activity of the immune system, it further destroys the central nervous system.

Abstract Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), depicted by lymphocytic infiltration and demyelination. MS is associated with the up-regulation of pro-inflammatory and down-regulation of anti-inflammatory cytokines. The purpose of this experimental study was to evaluate the expression level of TGF-β1, TGF-β 2, TGF-β-R1, and TGF-β-R2 mRNAs in peripheral blood mononuclear cells (PBMCs) from MS patients and healthy controls using Real-Time PCR. Our findings indicated that the TGF-β-R1 expression level was 2.25 times higher in controls than in MS patients. Also, a significant correlation between normalized expression of TGF-β-R1 and TGF-β1, or TGF-β2 was observed. Therefore, these genes could likely play an important role in the etiology of MS.

Abstract Multiple sclerosis (MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Epstein–Barr virus (EBV) is a human DNA herpesvirus infecting more than 90% of the world's population. EBV is the etiological agent of infectious mononucleosis (Pfeiffer's disease). Major predisposing factors for MS are certain tissue types (e.g., HLA DRB1*15:01), vitamin D deficiency, smoking, obesity, and infection with Epstein-Barr virus (EBV). This review summarizes current knowledge on the association between EBV and MS.

Abstract The roles of miRNAs in autoimmunity are only beginning to be explored; they may be involved in regulating immune responses against self-tissues.miRNAs may contribute to disease progression and response to treatment in MS patients. Several studies on MS have analyzed the role or profile of miRNAs in different tissues including peripheral blood mononuclear cells (PBMCs).The current study evaluated mir-21 and mir-146a in CSF samples of patients with multiple sclerosis. Differential expression of the two miRNAs was detected in at least 80% of the CSF samples;however, additional functional studies and analyses of larger cohorts are needed to validate these results and to elucidate the real role of these miRNAs in the context of MS.
 

Abstract Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder. The etiology of MS is not clear but genetic and epigenetic factors are involved in MS development. Studies have shown that IL7R gene polymorphisms is capable of changing MS susceptibility. We investigated the association of MS with rs11567658, rs11567686 promoter polymorphisms of IL7R gene in western provinces of Iran. In the present study, 187 MS patients and 190 healthy control were evaluated. Polymorphic regions of IL7R promoter were amplified by appropriated primers and polymorphisms were then evaluated by RFLP method followed by validation via Sanger sequencing. Results shown rs11567685 and rs11567686 are significantly associationed with MS (P = 0.017 P = 0.046), significant association of these polymorphism with age was also found (P = 0.002). This study showed that IL7 receptor gene polymorphism has a key role in MS development and may be important opportunity for development of therapeutic and diagnostic strategies in context of personalized medicine.