Sclerosis

Background: Falls are common among individuals with multiple sclerosis (MS), yet standard clinical mobility assessments—such as the Timed Up and Go (TUG)—may not fully capture the complexities of real-world ambulation, leading to suboptimal fall identification. There is a critical need to evaluate the ecological validity of these assessments and identify alternative tests that better reflect real-world mobility and more accurately detect falls. This study examined the ecological validity of the TUG and novel dual-task clinical assessments by comparing laboratory-based gait metrics to community ambulation in individuals with MS and evaluated their ability to identify fallers. Methods: Twenty-seven individuals with MS (age 59.11 ± 10.57) completed the TUG test and three novel dual-task mobility assessments (TUG-extended, 25-foot walk and turn, and Figure 8 walk), each performed concurrently with a phonemic verbal fluency task. After lab assessments, the participants wore accelerometers for three consecutive days. Gait speed and stride regularity data was collected during both the in-lab clinical assessments and identified walking bouts in the community. The participants were stratified as fallers or non-fallers based on self-reported fall history over the previous six months. Findings: Significant differences were observed between the TUG and real-world ambulation for both gait speed (p < 0.01) and stride regularity (p = 0.04). No significant differences were found in gait metrics between real-world ambulation and both the 25-foot walk and turn and TUG-extended. Intraclass correlation coefficient analysis demonstrated good agreement between the 25-foot walk and turn and real-world ambulation for both gait speed (ICC = 0.75) and stride regularity (ICC = 0.81). When comparing the TUG to real-world ambulation, moderate agreement was observed for gait speed (ICC = 0.56) and poor agreement for stride regularity (ICC = 0.41). The 25-foot walk and turn exhibited superior predictive ability of fall status (AUC = 0.76) compared to the TUG (AUC = 0.67). Conclusions: The 25-foot walk and turn demonstrated strong ecological validity. It also exhibited superior predictive ability of fall status compared to the TUG. These findings support the 25-foot walk and turn as a promising tool for assessing mobility and fall risk in MS, warranting further study. Full article

Introduction: Walking is perceived as the most important bodily function for persons with multiple sclerosis (pwMS) and is impaired in more than 70% of pwMS. In addition, the effect of multiple sclerosis (MS) on gait pattern increases in fast walking and during fatiguing exercises, altering the spatiotemporal gait parameters and walking reserve. Objectives: The objective of this study is to investigate the impact of a 12 min intermittent-walking protocol on spatiotemporal gait parameters and on the fatigability of pwMS, as well as the association with perceived exertion and reported symptoms of fatigue. Methods: Twenty-six persons with relapse-remitting MS and twenty-eight healthy controls (HCs) were included in this cross-sectional study. The Modified Fatigue Impact Scale and the Symbol Digit Modality Test were used to evaluate fatigue symptoms and cognitive function, respectively. Participants walked six times during an uninterrupted 2-min period. Before, during the rest periods and after the last 2 min walk, the rate of perceived exertion (RPE) was measured using the Borg Scale, and the spatiotemporal gait parameters were assessed with GaitRite. The cut-off value of 10% deceleration of the distance walked index classified pwMS into two groups: MS Fatigable (MS-F) and MS Non-Fatigable (MS-NF). One-way and two-way Analyses of variance (ANOVAs) were used to verify the effect of time and groups, respectively. Results: PwMS walked slower, travelled shorter distances, and presented shorter step lengths compared to HCs. No effects of the intermittent-walking protocol were found for all pwMS, but the MS-F group had deteriorated walking speed, step length, and cadence. Walking dysfunction was associated with perceived fatigability, reported symptoms of fatigue, cognitive function, and disability. Reported symptoms of fatigue was associated with perceived exertion but not with performance fatigability. Conclusions: Changes in gait parameters were weak to moderately associated with performance fatigability and the perception of effort and disability but not with reported fatigue symptoms, highlighting distinct constructs. The walking speed reserve and step length reserve also emerged as potential early markers of performance decline. Full article

Systemic sclerosis (SSc) is a multifaceted autoimmune disease in which the complex interplay of genetic predisposition and environmental factors triggers aberrant immune responses, ultimately leading to vasculopathy and fibrosis. This review offers a comprehensive overview of current perspectives on SSc pathogenesis, integrating classical concepts with recent breakthroughs enabled by advanced analytical techniques. We delve into the foundational trans-organ pathophysiology of SSc, encompassing epigenetic dysregulation, chronic inflammation, vascular injury, vasculopathy, and fibrosis. Furthermore, we explore the organ-specific modifiers that contribute to the heterogeneity of SSc manifestations across different organ systems, including the skin, gastrointestinal tract, lungs, and heart. Recent studies employing single-cell transcriptomics, spatial proteomics, and epigenomic profiling are highlighted, demonstrating how these technologies are revolutionizing our understanding of SSc cellular and molecular pathology. This evolving landscape of SSc pathogenesis research is critical for identifying novel therapeutic targets and advancing personalized medicine approaches for SSc patients. Full article

Background/Objectives: Late-onset multiple sclerosis (LOMS), characterized by an onset of disease at ≥50 years, is a distinct subset of multiple sclerosis (MS) with unique clinical and demographic features. While environmental factors such as smoking, diet, infections, and air pollution are well-studied in regard to early-onset MS, their roles in LOMS are not fully understood. This systematic review evaluates the environmental and clinical factors associated with LOMS risk to provide insights for prevention and management. Methods: A systematic review of MEDLINE, EMBASE, Web of Science, and Cochrane Library was conducted in accordance with PRISMA guidelines. Four studies (one case–control study, two cohort studies, and one cross-sectional study) investigating substance use, diet, disease-modifying therapies (DMTs), and demographic factors were included. Study quality was assessed using the Newcastle–Ottawa Scale (NOS), and findings were synthesized narratively. Results: Substance use, including smoking and the use of alcohol and drugs, was significantly associated with an increased LOMS risk (ORs 1.9–3.2). Diet quality showed no significant association with LOMS risk (HR = 1.02, 95% CI: 0.85–1.22). DMTs reduced disability progression (OR = 0.67, 95% CI: 0.55–0.81) and mortality (HR = 0.78, 95% CI: 0.65–0.94). Regional variations in symptoms were noted, with optic neuritis frequently reported as an initial symptom. Conclusions: This review identifies substance use as a significant modifiable risk factor for LOMS, while DMTs improve outcomes by reducing disability progression and mortality among elderly MS patients. The neutral findings for diet quality suggest a limited role in LOMS prevention. Further research is needed to explore broader environmental exposure and longitudinal outcomes to enhance understanding and management of LOMS. Full article

The mortality risk in systemic sclerosis (SSc) is primarily determined by pulmonary involvement (interstitial lung disease (ILD), pulmonary fibrosis), pulmonary arterial hypertension (PAH), and cardiac involvement. With timely and intensive treatment, the disease can be halted or even improved. Therefore, early diagnosis remains crucial. Unfortunately, biomarkers currently available cannot meet this requirement. SSc is characterized by autoimmune inflammation, vasculopathy, and fibrosis. The immunometabolic characterization of autoimmune diseases contributes to a better understanding of the underlying inflammatory processes. In this narrative review, we included 13 studies on metabolomic patterns in SSc in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA). Current studies indicate an altered metabolome in SSc. All documented significant differences between patients with SSc and healthy controls, although the observed metabolomic patterns in SSc were inconsistent between studies. Metabolome alterations include, in particular, energy-related metabolic pathways such as glycolysis/gluconeogenesis, including the synthesis and degradation of ketones, fatty acid oxidation, amino acid-related metabolic pathways, lipid metabolism, and the tricarboxylic acid (TCA) cycle, including pyruvate metabolism. The most frequently examined organ complications with reported significant aberrations of the metabolome were skin involvement, ILD, and PAH. Conclusion: The detailed characterization of the SSc-specific metabolome promises a more comprehensive understanding of the pathogenic mechanisms of the disease. Furthermore, the detection of associations between specific metabolic aberrations and disease phenotypes bears hope for new biomarkers and an improved personalized approach to diagnostics, therapy, and follow-up in the management of SSc. Full article

Background: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vasculopathy, autoimmunity, and fibrosis. Due to its low prevalence and heterogeneous clinical presentation, early diagnosis remains challenging, often delaying appropriate treatment. The disease progresses from microvascular dysfunction, manifesting as Raynaud’s phenomenon, to systemic fibrosis affecting multiple organs, including the lungs, gastrointestinal tract, heart, and kidneys. There have been considerable advancements in understanding the pathophysiology of the disease during the last few years and this has already resulted in the improvement of the therapeutic approaches used to control organ-specific manifestations. However, the underlying cause of the disease still remains incompletely elucidated. Methods: Here, we summarize the current knowledge on the SSc pathogenesis. Results: The pathophysiology involves an interplay of chronic inflammation, impaired vascular function, and excessive extracellular matrix deposition, leading to progressive organ damage. Endothelial dysfunction in SSc is driven by immune-mediated injury, oxidative stress, and the imbalance of vasoconstrictors and vasodilators, leading to capillary loss and chronic hypoxia. Autoantibodies against endothelial cells or other toxic factors induce apoptosis and impair angiogenesis, further exacerbating vascular damage. Despite increased angiogenic factor levels, capillary repair mechanisms are defective, resulting in progressive ischemic damage. Dysregulated immune responses involving Th2 cytokines, B cells, and macrophages contribute to fibroblast activation and excessive collagen deposition. Transforming growth factor-beta (TGF-β) plays a central role in fibrotic progression, while fibroblasts resist apoptosis, perpetuating tissue scarring. The extracellular matrix in SSc is abnormally stiff, reinforcing fibroblast activation and creating a self-perpetuating fibrotic cycle. Conclusions: Advances in molecular and cellular understanding have facilitated targeted therapies, yet effective disease-modifying treatments remain limited. Future research should focus on precision medicine approaches, integrating biomarkers and novel therapeutics to improve patient outcomes. Full article

Background: Amyotrophic lateral sclerosis (ALS) is a rare, incurable, and fatal neurodegenerative disease that affects the muscles and results in paralysis. The onset and development of ALS involve complex interactions among metabolic signaling, genetic pathways, and external factors (epigenetics). New biomarkers and alternative therapeutic targets have been suggested; nonetheless, the results have been unsatisfactory. Mutations in SOD1, fused in sarcoma (FUS), and TAR DNA-binding protein 43 (TDP-43) have been identified in sporadic amyotrophic lateral sclerosis and approximately 12–20% of familial amyotrophic lateral sclerosis (fALS). Aim: This review analyzes dysregulated microRNA signaling pathways and their interactions with metabolic pathways in the context of ALS progression. Significance: Despite this, biomarkers remain unreliable, and the current medications prolong life without providing a cure. Some proposed approaches to control ALS progression include balancing autophagy and apoptosis, eliminating aggregated proteins, addressing mitochondrial dysfunction, and reducing inflammation. There is a need for studies on new biomarkers, medications, and therapeutic targets. In this context, deregulated circulating microRNAs are attracting attention for new studies on ALS at various phases of the disease. Despite the extensive literature on microRNAs as potential biomarkers for ALS, the proposition for translational clinical use remains limited. Studies have indicated a significant downregulation or upregulation of microRNAs in the motor neurons of ALS patients compared with those with other neurodegenerative disorders and healthy controls. The microRNA biogenesis highlights the importance of this study. MicroRNAs regulate protein synthesis (translation); all human cells express many microRNAs. The complementary structures of microRNA sequences and their mRNA targets allow them to significantly alter cellular and physiological processes. Studies have examined these microRNAs as potential biomarkers for several physiological states and diseases. Comments: The success of these studies may lead to simple, low-cost, and efficient solutions for controlling the progression of ALS and other degenerative diseases. As a result, it is challenging to identify a specific biomarker with total reliability, as a specific microRNA that is increased in one disease phase can decrease in another. These points require careful consideration. They exhibit several complexities and varied interactions, focusing on mRNA targets. The current critical review highlights the potential of microRNAs as biomarkers for diagnosis, prognosis, and therapeutic options in ALS, and raises several points for discussion. Conclusions: The current critical review highlights the potential of microRNAs as biomarkers for diagnosis, prognosis, and therapeutic options in ALS, and raises several points for discussion. Full article

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system affecting over 2.8 million people around the world. Artificial intelligence (AI) is becoming increasingly utilised in many areas, including patient care for MS. AI is revolutionising the diagnosis and treatment of MS by enhancing the accuracy and efficiency of both processes. AI algorithms, particularly those based on machine learning, are being used to analyse medical imaging data, such as MRI scans, to detect early signs of MS, monitor disease progression and assess patient treatment response with greater precision. AI can help identify subtle changes in the brain and spinal cord that may be missed by human clinicians, leading to earlier diagnosis and more personalised treatment plans. Additionally, AI is being employed to predict disease outcomes, which could allow clinicians to tailor therapies for individual patients based on their unique disease characteristics. In drug development, AI is accelerating the identification of potential therapeutic targets and the optimisation of clinical trial designs, potentially leading to faster development of new treatments for MS. AI is also playing a critical role in MS fundamental research by promoting efficient analysis of vast amounts of single-cell data. Through these advancements, AI could improve the overall management of MS, offering more timely interventions and better patient outcomes. In this review, we discuss these topics and whether the influence of AI on diagnosis, treatment and research of MS can change the future of this field. Full article

Introduction: Cognitive impairment (CI) is recognized as a very frequent feature of persons with multiple sclerosis (pwMSs). Multiple studies have demonstrated the effectiveness of cognitive rehabilitation (CR) in improving CI linked to cerebral functional connectivity facilitation and increased strategies to cope with daily living activities. Nevertheless, there is considerable heterogeneity in the methodologies and protocols proposed to pwMSs. Aim: This study aimed to establish a current state of CR for pwMSs, among different types of healthcare providers (HCPs) in France. Methods: A Web-based survey was conducted between March and September 2024 among HCPs involved in the care of pwMSs. Results: One hundred and one HCPs involved in the care of pwMSs participated in this survey. CR was considered efficient by 97% of HCPs, especially when multimodal. Based on the responses, CR is proposed mainly following cognitive complaints, for moderate or severe cognitive disorders, and at the onset of the disease (45%). HCPs mentioned several obstacles to the implementation of CR, notably the cost of remediation (37%), and the lack of availability of both professionals (58%) and patients (51%). Conclusions: This rehabilitation requires specific tools combined with psychoeducative advice provided by multidisciplinary HCPs. Full article

Multiple sclerosis (MS) is a chronic and incurable neurological disease of the central nervous system. Three main forms of the disease have been distinguished: relapsing–remitting form (RRMS), secondary progressive form (SPMS), and primary progressive form (PPMS). Currently, in patients with MS, in addition to pharmacotherapy, neurorehabilitation is indicated to improve the motor function of the body and action in the most physiological movement patterns possible. In this therapy, work on lost or incorrect functions is used to provide the patient with self-sufficiency in everyday life. Kinesiotherapy is used as part of neurorehabilitation. This therapy for MS includes coordination exercises aimed at facilitating movement, strengthening exercises and resistance training, balance exercises, improving stability during everyday activities stretching and relaxation exercises, improving tissue elasticity, reducing tension, and breathing exercises. In this article, we present various possibilities for using kinesiotherapy in patients with MS at various stages of disease development. Moreover, we would like to draw attention to the benefits of physical activity leading to a significant improvement in the quality of life in MS patients. We believe that a regular exercise program should be part of the neurorehabilitation program in these patients in the future. Full article

Behavioral activation therapy (BAT) was initially developed to treat depression and was subsequently extended as a transdiagnostic therapy for other psychiatric and neurocognitive disorders. However, research on its impact in people with multiple sclerosis (MS) is lacking. We suggest that MS-adapted BAT reduces neuropsychiatric symptoms, neurocognitive impairment, social isolation, and impairment of activities of daily living—key components of MS-related quality of life. Our proposed adaptation of the traditional therapy includes a focus on increasing engagement in cognitive, physical, or social activities (activity demand characteristics) to improve cognition and daily life function. In addition, these activities should be individually perceived as energizing, relaxing, or meaningful (subjective activity characteristics) to benefit neuropsychiatric symptoms and social connectedness. Finally, we propose that BAT in MS should specifically focus on reducing stressful activities (i.e., unenjoyable, high-arousal activities) and increasing relaxing activities (i.e., enjoyable, low-arousal activities), as this dimension might tackle the neuroinflammatory etiology of MS. Full article

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by vasculopathy, immune dysregulation, and progressive fibrosis affecting the skin and internal organs. Pulmonary complications, including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), are major contributors to morbidity and mortality, while skin fibrosis remains a hallmark of disease heterogeneity. Despite advances in understanding SSc pathogenesis, early diagnosis and timely therapeutic intervention remain challenging due to the rapid progression of inflammation and the narrow window before irreversible fibrosis occurs. The identification of reliable biomarkers is crucial for improving diagnosis, monitoring disease activity, and guiding treatment decisions in SSc. While autoantibodies are well-established diagnostic tools, this review focused on non-autoantibody biomarkers, including soluble proteins, cytokines, chemokines, epigenetic modifiers, and oxidative stress indicators. These biomarkers reflect diverse pathogenic mechanisms such as endothelial injury, fibroblast activation, immune signaling, and extracellular matrix remodeling. By examining the available evidence across both clinical and preclinical studies, this review provides an updated overview of molecular markers involved in inflammation and fibrosis in SSc. Understanding their biological significance and therapeutic potential may improve risk stratification, guide targeted interventions, and ultimately contribute to the development of precision medicine strategies in systemic sclerosis. Full article

Background/Objectives: Health locus of control (LOC) refers to one’s perceptions of who or what controls one’s health. Recent evidence has found that chance LOC (CLOC) is associated with improved quality of life (QoL) in multiple sclerosis (MS). The purpose of the current study was to identify mediators and moderators of the LOC-QoL relationship in MS. Methods: For this study, 5266 participants with MS completed a questionnaire pack that included the Multidimensional Health Locus of Control Scale, the Unidimensional Self-Efficacy Scale for MS (USE-MS), and the World Health Organization Quality of Life Scale—BREF (WHOQoL-BREF). The relationship between LOC and QoL was examined within a structural equation model (SEM). Results: In the total sample, self-efficacy was found to fully mediate the relationship between LOC and QoL for both internal (ILOC) and CLOC orientations. Powerful others LOC (PLOC) had no association with QoL. The same results were found for the relationship of LOC to functioning. In the secondary progressive MS subgroup, the relationship between CLOC and QoL was only partially mediated by self-efficacy. Conclusions: LOC influences QoL through its impact on self-efficacy, one of several potentially mediating factors between LOC and QoL in MS. Disability did not moderate the associations of LOC, but moderation of the CLOC-QoL relationship by disease subtype was found. Psychological training to improve self-efficacy in MS may be particularly useful in those subgroups where LOC-QoL is largely mediated by self-efficacy. Full article

Introduction: Approximately 80% of individuals with multiple sclerosis (MS) have a positive response to autologous hematopoietic stem cell transplantation (aHSCT). Markers that may predict the transplant outcome are necessary. The objective of this work is to identify markers that may refine the selection of patients with multiple sclerosis who could benefit from aHSCT. Methods: We evaluated the levels of six biomarkers in the peripheral blood of patients with MS before aHSCT. The design of this study is cross-sectional; patients were divided into two transplant-responses-at-12-months groups, responders (ΔEDSS < 0) and non-responders (ΔEDSS > 0). Pre-transplant samples were used to assess the different markers. Results: Thirty-four patients were enrolled: fourteen were non-responders and twenty were responders to aHSCT. Among the evaluated biomarkers, a significant difference was only detected in miR-146a levels, with increased values in the non-responder group. Conclusions: The biomarker miR146a could be useful to evaluate the response to aHSCT in patients with MS. Full article

Background/Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive degeneration of motor neurons. The gut microbiota, a community of microorganisms in the digestive tract, has recently been implicated in ALS pathogenesis through its influence on neuroinflammation and metabolic pathways. This review explores the potential role of digestive microbiota and its metabolites in ALS progression and investigates therapeutic approaches targeting gut microbiota. Methods: A comprehensive review of the current literature was conducted to assess the relationship between gut microbiota composition, microbial metabolites, and ALS progression in patients. We searched for published reports on microbiota composition, microbial metabolites, and ALS, emphasizing the complex interplay between dysbiosis, neuroinflammation, and systemic metabolism. Special emphasis was placed on studies exploring short-chain fatty acids (SCFAs), bacterial amyloids (curli-like factors), and neurotoxins such as β-methylamino-L-alanine (BMAA). The role of the liver–gut axis was evaluated as well. The potential changes in microbiota would sustain the rationale for therapeutic strategies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary interventions. Results: ALS patients exhibit gut dysbiosis, characterized by reduced SCFA-producing bacteria and an increase in potentially pathogenic genera. Of note, different studies do not agree on common patterns of microbiota being linked to ALS, supporting the need for further, more extensive studies. Dysbiosis sometimes correlates with systemic inflammation and disrupted liver function, amplifying neuroinflammatory responses. Key microbial metabolites, including SCFAs, bacterial amyloids, and BMAA, may exacerbate motor neuron degeneration by promoting protein misfolding, oxidative stress, and neuroinflammation. Emerging therapeutic strategies, including probiotics and FMT, show potential in restoring microbial balance, although clinical data in ALS patients remain limited. Conclusions: The gut microbiota could modulate neuroinflammation and systemic metabolism in ALS. Microbiota-targeted therapies, such as probiotics and dietary interventions, represent promising avenues for mitigating disease progression. Further research is required to validate these interventions through large-scale, longitudinal studies and to develop personalized microbiota-based treatments tailored to individual ALS phenotypes. Full article

Background: The 2011 Very Early Diagnosis of Systemic Sclerosis (VEDOSS) criteria include both patients at risk of progression and those with mild non-progressive forms of SSc. Early diastolic and systolic dysfunction can indicate myocardial fibrosis in SSc patients, yet data on myocardial impairment in the VEDOSS population are limited. Objectives: This study aimed to identify subclinical echocardiographic changes and predictive markers of cardiac dysfunction in both very early and mild-longstanding forms of VEDOSS. Methods: We conducted a cross-sectional observational study involving 61 patients meeting VEDOSS criteria followed up regularly within our Scleroderma referral center. Patients were categorized as early VEDOSS (e-VEDOSS) or mild-longstanding VEDOSS (ml-VEDOSS) based on disease duration (≥10 years). We analyzed clinical and demographic data, focusing on echocardiographic parameters such as the E/A ratio and left ventricular (LV) thickness. Statistical analyses included chi-square, Fischer exact, and student’s t tests, with a significance threshold of p < 0.05. Results: ml-VEDOSS patients were older and reported a higher burden of comorbidities. Autoantibody-positive patients exhibited lower E/A ratios and increased left atrial size. Late nailfold videocapillaroscopic pattern patients exhibited increased PWED thickening and aortic valve insufficiency. Notably, patients undergoing vasodilators experienced larger right atrial volume, while patients receiving Renin-Angiotensin-Aldosterone System (RAAS) inhibitors reported reduced E/A ratio. Multivariable analysis confirmed DLCO% as the sole predictor of both diastolic and systolic impairment in VEDOSS population. Conclusions: Careful monitoring of cardiac function in VEDOSS patients is crucial as subclinical alterations may occur even in the absence of symptoms. DLCO% emerged as an important predictor of LV diastolic dysfunction. Full article

Apolipoprotein L1 (APOL1) genetic variations, notably the G1 and G2 alleles, have important roles in the pathophysiology of focal segmental glomerulosclerosis (FSGS) and other kidney problems, especially in people of African descent. This review summarizes current understanding about the genetic, molecular, and clinical features of APOL1-associated FSGS and investigates new therapeutic options. It reveals how APOL1 mutations generate kidney injury through mechanisms such as podocyte dysfunction, mitochondrial impairment, and dysregulated inflammatory networks. Recent treatment developments, such as small-molecule inhibitors like inaxaplin, antisense oligonucleotides, and novel interventions targeting lipid metabolism and inflammatory pathways, are being assessed for their capacity to address the specific issues presented by APOL1-associated nephropathy. We also address gaps in knowledge, such as the function of environmental triggers and the systemic consequences of APOL1 mutations, emphasizing the significance of targeted research. Full article

Background: Systemic sclerosis (SSc), also known as scleroderma, is a complex, chronic autoimmune disease characterized by fibrosis of the skin and internal organs, vasculopathy, and immune system dysregulation. The treatment of SSc has historically focused on symptom management and slowing down disease progression through conventional immune-suppressive agents. New therapeutic approaches have been emerging due to advances in understanding of the disease mechanisms, particularly in the areas of fibrosis, vascular involvement, and immune dysregulation. Methods: In this review of the literature, we discuss the current stage of development of B-cell-depleting immune therapies in SSc. Results: B-cell depletion therapy has become an area of growing interest in the treatment of SSc due to the role played by B cells in the pathogenesis of the disease. There is increasing evidence that B cells contribute to disease progression through multiple mechanisms. B cells in SSc are implicated in autoantibody production, cytokine production, and fibroblast activation. B cells are responsible for producing autoantibodies, such as anti-topoisomerase I (Scl-70) and anti-centromere antibodies, which are hallmarks of SSc. B cells release pro-inflammatory cytokines (such as interleukin-6 [IL-6] and transforming growth factor β [TGF-β]), which promote fibrosis and inflammation, they also contribute to the activation of fibroblasts, the cells responsible for excessive collagen production and fibrosis, a key feature of SSc. Conclusions: In light of these findings, therapies that target B cells are being investigated for their potential to modify the disease course in SSc, particularly by reducing autoantibody production, inflammation, and fibrosis. Full article

Background: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelination in the central nervous system (CNS). Despite the availability of interventions for disease exacerbations and symptomatic management, EM remained without a cure. Oxidative stress has been implicated in the MS demyelination mechanism. Adjuvant therapies like α-lipoic acid (ALA) have garnered interest for their potential to mitigate oxidative damage and control MS symptoms. ALA is found naturally in vegetables and red meat and can also be synthesized in mitochondria through enzymatic reactions involving octanoic acid and cysteine. However, its bioavailability from dietary sources is limited, prompting an investigation into supplemental forms. We conducted a systematic review and meta-analysis to assess the effect of ALA on disability in randomized clinical trials (RCTs) for MS. Methods: Records were searched until June 2023 (CRD42023397760). Five RCTs evaluated ALA’s effect on MS progression using the Expanded Disability Status Scale (EDSS). The quality of evidence was assessed using GRADE, and publication bias was evaluated using Egger’s and Begg’s tests. Results: Following the selection process, five studies were included involving 179 patients (87 placebo and 92 ALA). Oral administration of racemic ALA (R/S-ALA) at 600 mg twice daily reduced EDSS, indicating a potential for ALA supplementation to mitigate MS disability. The North American trials (SPMS patients) did not show heterogeneity, while Asian studies (RRMS patients) were moderated. The quality of evidence was high without publication bias. Conclusions: ALA treatment reduce EDSS scores. However, further studies are warranted to establish the role of ALA as an adjuvant in clinical practice in long-term follow-up (>2 years) RCTs. Full article