Sclerosis, Volume 2, Issue 3 (September 2024) – 7 articles

Apart from the significant progress the scientific community has made during the last few decades, inflammation-mediated kidney-related diseases like chronic and diabetic kidney diseases (CKD and DKD) and glomerulosclerosis still continue to raise mortality rates. Recently, conventional therapeutic interventions have been put aside, since natural vitamin D-derived treatment has gained attention and offered several promising outcomes. Within this article, the utilization of vitamin D and its analogues as potential treatment toward kidney-related diseases, due to their anti-inflammatory, antioxidant and anti-fibrotic activity, is outlined. Vitamin D analogues including calcitriol, paricalcitol and 22-oxacalcitriol have been previously explored for such applications, but their hidden potential has yet to be further elucidated. Several clinical trials have demonstrated that vitamin D analogues’ supplementation is correlated with inflammatory signaling and oxidative stress regulation, immunity/metabolism augmentation and subsequently, kidney diseases and healthcare-related infections’ prevention, and the results of these trials are thoroughly evaluated. The highlighted research outcomes urge further study on a plethora of vitamin D analogues with a view to fully clarify their potential as substantial anti-inflammatory constituents of renal diseases-related treatment and their health-promoting properties in many kidney-associated healthcare complications and infections. Full article

Systemic sclerosis (SSc) is a rare, multifactorial autoimmune disease characterized by widespread vascular damage and fibrosis. Pulmonary involvement is a significant manifestation of SSc, contributing to considerable morbidity and mortality. Therefore, identifying reliable biomarkers is of the utmost importance. This review explores emerging biomarkers to enhance diagnostic accuracy, prognostic assessment, and disease monitoring in SSc lung involvement. We discuss recent findings in immunological biomarkers, inflammatory indicators, and other parameters that can function as potential diagnostic and prognostic tools. A comprehensive understanding of these biomarkers could result in earlier and more accurate detection of pulmonary complications in SSc, aiding in timely intervention. Furthermore, we explore the advances in disease monitoring through innovative biomarkers, focusing on their roles in disease activity and treatment response. Integrating these novel biomarkers into current clinical practice and therapeutic protocols through clinical trials can revolutionize the management of SSc-related lung disease, ultimately improving patient outcomes and quality of life. Full article

Multiple sclerosis (MS) is associated with a high prevalence of emotional disorders affecting the health-related quality of life of patients and their families. Pseudobulbar affect (PBA), also referred to as pathological laughing and crying, is an under-recognized and under-treated co-morbidity. We conducted a systematic literature review of 16 studies to determine the prevalence and clinical characteristics of PBA in patients with MS of all ages. Based on conservative figures available from 8/16 studies, the prevalence of PBA in the context of MS was found to range between 2% and 10% (median 10%), with higher percentages in the female population. Possible reasons for the observed variability in the prevalence data include heterogeneity of the diagnostic methodologies and common presence of confounding factors, such as co-morbid affective disorders. The clinical presentation was found to be comparable to that of PBA in the context of other neurological disorders, as it reflected the location of underlying lesions (especially in the brainstem) rather than the associated pathology. Clinicians should be prompted to consider PBA in the differential diagnosis of emotional disorders in the context of MS by using both clinical criteria and psychometric instruments. Further studies should be conducted to develop standardized diagnostic protocols and to optimize therapeutic approaches for the clinical management of this patient population. Full article

Background: This systematic review searched to identify a potential biomarker in serum/plasma or cerebrospinal fluid (CSF) to differentiate between relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). There is currently no definitive method for determining whether a patient is in the RRMS course or has converted to the SPMS course. A biomarker could therefore aid the clinician to make this diagnosis. The aim of this study is to assess if there are biomarkers or combinations of biomarkers in serum/plasma or CSF that can detect secondary progression in multiple sclerosis at an early stage. Methods: The PubMed and EMBASE databases were searched to identify relevant studies. Both MeSH terms and text words in the title/abstract were used in both search strategies. The method included forward and backward citation searches. A risk of bias tool was used to assess all the studies that were included. Results: A total of 7581 articles were identified from the initial search. Additionally, 3386 articles were added after the citation search. Of these, 39 articles fulfilled the inclusion criteria and none of the exclusion criteria. The review investigated 28 different biomarkers in CSF and serum/plasma. Discussion: Of the 28 different biomarkers, six biomarkers appeared to be the most promising: neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), Galectin-9, YKL-40/CHI3L1, osteopontin, and MCP-1. This review provides new insights into potential directions for future studies to investigate biomarkers as a diagnostic tool for SPMS. Full article

Emerging evidence links dietary interventions to favorable multiple sclerosis (MS) outcomes; however, evidence for the efficacy of dietary interventions on functional disability remains sparse. Data from two 12-week, randomized, controlled pilot trials were pooled to investigate the efficacy of a modified Paleolithic diet (Paleo) on functional disability, as assessed by the MS Functional Composite (MSFC), among people diagnosed with MS. Pooled baseline-referenced MSFC scores were calculated from the nine-hole peg test (NHPT), timed 25-foot walk (T25FW), and Paced Auditory Serial Addition Test (PASAT) Z-scores. There was no significant difference in the mean change in MSFC scores between groups (p = 0.07). In the Paleo group, a significant increase was observed in the MSFC scores (p = 0.03), NHPT (p < 0.001), and PASAT (p = 0.04) Z-scores at 12 weeks, indicating reduced functional disability compared to baseline values. No significant changes were observed within the Control group. Study-specific differences in the MSFC changes between groups were observed. Functional disability was reduced compared to the baseline in the Paleo group, possibly depending on MS type. These results provide preliminary observations on the efficacy of a modified Paleolithic diet for reducing or maintaining functional disability in MS. Full article

Background: Amyotrophic Lateral Sclerosis (ALS) is a debilitating neurodegenerative disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness and paralysis. Understanding the molecular basis of ALS is crucial for the development of effective therapies. Objective: This study aims to explore the genetic and epigenetic underpinnings of ALS, focusing on the interplay between gene mutations, protein interactions, and epigenetic factors. Methods: We conducted an extensive analysis of key ALS-associated genes including TARDBP, SOD1, ANG, VAPB, and CHMP2B. We used computational tools to assess the functional consequences of identified mutations on neuronal health and explored DNA methylation patterns in gene promoters to investigate epigenetic regulation. Results: Our findings reveal that mutations in ALS-associated genes disrupt critical processes such as amyloid fibril formation and autophagy. We also identified altered DNA methylation patterns, suggesting a mechanism for changes in gene expression linked to ALS. Molecular docking studies highlighted Humulene and Buddledin C as compounds with high binding affinities to the SOD1 enzyme, suggesting their potential to mitigate hallmark features of ALS pathology such as SOD1 aggregation and oxidative stress. Conclusions: Our comprehensive analysis underscores the complexity of ALS pathogenesis, combining genetic, epigenetic, and proteomic approaches. The insights gained not only enhance our understanding of ALS but also pave the way for novel therapeutic strategies, highlighting the importance of integrated approaches in tackling this challenging neurodegenerative disease. Full article

Multiple sclerosis (MS) is an inflammatory demyelinating disease affecting the central nervous system (CNS). In MS, oligodendrocytes and myelin that surround axons to facilitate transmission of neuronal signals are destroyed by adaptive and innate immune cells, resulting in the formation of demyelinating plaques. For many years, research into MS pathophysiology has identified immune cell populations in lesions such as T cells, B cells, and myeloid and innate lymphoid cells. In this review, we discuss the involvement of these immune cells in MS pathophysiology and demonstrate how findings from histopathology studies and single-cell analyses in animal and human models have identified which immune cell subsets contribute to disease. This knowledge has facilitated the introduction of numerous immune-targeted therapeutics towards CD20, CD52, interferon-beta, sphingosine-1-phosphate receptor, Bruton’s tyrosine kinase, and many more. These treatments have shown effective reduction in new lesion formation and management of symptoms in MS patients. Furthermore, as MS is a chronic disease, these therapeutics slow disease progression, reduce cognitive disabilities, and prevent relapses. Further research is required to develop a cure for MS with limited side effects. The ongoing research that utilises innovative methods to identify and assess MS pathophysiology could transform the treatment landscape for patients in the future. Full article