Treatment Of Multiple Sclerosis Research Articles

Hybrid derivatives containing dimethyl fumarate and benzothiazole scaffolds for the potential treatment of multiple sclerosis; in silico & in vivo study.

Multiple Sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the CNS. Riluzole and dimethyl fumarate (DMF) are two FDA-approved drugs to treat amyotrophic lateral sclerosis (ALS) and MS. Riluzole (a benzothiazole derivative) inhibits glutamate release from nerve terminals by antagonizing the N-Methyl-D-Aspartate (NMDA) receptor, and DMF upregulates anti-oxidative pathways. Herein, using molecular hybridization strategy, we synthesized some new hybrid structures of Riluzole and DMF through some common successive synthetic pathways for evaluating their potential activity for remyelination in MS treatment. Molecular docking experiments assessed the binding affinity of proposed structures to the NMDA active site. The designed structures were synthesized and purified based on well-known chemical synthesis procedures. Afterward, in vivoevaluation for their activity was done in the C57Bl/6 Cuprizone-induced demyelination MS model. The proposed derivatives were recognized to be potent enough based on docking studies (ΔGbind of all derivatives were -7.2 to -7.52 compare to the Ifenprodil (-6.98) and Riluzole (-4.42)). The correct structures of desired derivatives were confirmed using spectroscopic methods. Based onin vivostudies, D4 and D6 derivatives exhibited the best pharmacological results, although only D6 showed a statistically significant difference compared to the control. Also, for D4 and D6 derivatives, myelin staining confirmed reduced degeneration in the corpus callosum. Consequently,D4 and D6derivatives are promising candidates for developing new NMDA antagonists with therapeutic value against MS disorders.

Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers. We focus on fingolimod, a small molecule drug that is FDA-approved for treatment of multiple sclerosis, which has also shown promise in the treatment of stroke. Unfortunately, fingolimod has poor solubility and very extensive partitioning to plasma proteins and RBCs (in whole blood, 86% partitions to RBCs, 13.96% to plasma proteins, and 0.04% is free). We develop a liposomal formulation that slows the partitioning of fingolimod to RBCs and plasma proteins, enables intravenous delivery, and additionally prevents fingolimod toxicity to RBCs. The liposomal formulation nearly completely prevented fingolimod adsorption to plasma proteins (association with plasma proteins was 98.4 ± 0.4% for the free drug vs. 5.6 ± 0.4% for liposome-loaded drug). When incubated with whole blood in vitro, the liposomal formulation greatly slowed partitioning of fingolimod to RBCs and also eliminated deleterious effects of fingolimod on RBC rigidity, morphology, and hemolysis. In vivo, the liposomal formulation delayed fingolimod partitioning to RBCs for over 30 min, a critical time window for stroke. Fingolimod-loaded liposomes showed improved efficacy in a mouse model of post-stroke neuroinflammation, completely sealing the leaky blood-brain barrier (114 ± 11.5% reduction in albumin leak into the brain for targeted liposomes vs. 38 ± 16.5% reduction for free drug). This effect was only seen for liposomes modified with antibodies to enable targeted delivery to the site of action, and not in unmodified, long-circulating liposomes. Thus, loading fingolimod into liposomes prevented partitioning to RBCs and associated toxicities and enabled targeted delivery. This paradigm can be used for tuning the blood distribution of small molecule drugs for the treatment of acute illnesses requiring rapid pharmacologic intervention.

Recommendations for the Treatment of Multiple Sclerosis in Family Planning, Pregnancy and Lactation in Switzerland: Immunotherapy

Recommendations for the Treatment of Multiple Sclerosis in Family Planning, Pregnancy and Lactation in Switzerland: Immunotherapy

The first global landscape analysis of multiple sclerosis research funding.

Multiple sclerosis (MS) is an immune-mediated central nervous system disorder and a growing global health challenge affecting nearly 3 million people worldwide. Incidence and prevalence continue to increase with no known cause or cure. Globally governments and non-profit organizations fund research toward better understanding of and treatments for multiple sclerosis. This study identified MS research projects funded between 2021 and 2023 by government and non-profit organization sources. Projects were described by type of scientific approach, Pathways to Cure research category (i.e. Stop, Restore, End), and other key characteristics. Over 2,300 MS research projects were identified through 16 non-profit MS organizations and 18 government databases. The overall global portfolio of these projects is valued at nearly one and a half billion Euros. The majority of projects were classified in the Stop category (60%). Research collaboration occurs in many forms among the research community; around 272 projects were reported to be co-funded. Global MS research collaboration will accelerate progress toward increased knowledge, effective treatments, improved health outcomes, and ultimately cures for MS. This landscape analysis highlights the current distribution of MS research investment between topics and begins to suggest where the MS community should focus to increase potential impact for current and future endeavors.

Kynurenines and Inflammation: A Remarkable Axis for Multiple Sclerosis Treatment

Kynurenines and Inflammation: A Remarkable Axis for Multiple Sclerosis Treatment

Broader anti-EBV TCR repertoire in multiple sclerosis: disease specificity and treatment modulation.

Epstein-Barr virus (EBV) infection has long been associated with the development of multiple sclerosis (MS). MS patients have elevated titers of EBV-specific antibodies in serum and show signs of CNS damage only after EBV infection. Regarding CD8+ T-cells, an elevated but ineffective response to EBV was suggested in MS patients, who present with a broader MHC-I-restricted EBV-specific T-cell receptor beta chain (TRB) repertoire compared to controls. It is not known whether this altered EBV response could be subject to dynamic changes, e.g., by approved MS therapies, and whether it is specific for MS. 1317 peripheral blood TRB repertoire samples of healthy donors (n=409), patients with MS (n=710) before and after treatment, patients with neuromyelitis optica spectrum disorder (n=87), myelin-oligodendrocyte-glycoprotein antibody-associated disease (n=64) and Susac's syndrome (n=47) were analyzed. Apart from MS, none of the evaluated diseases presented with a broader anti-EBV TRB repertoire. In MS patients undergoing autologous hematopoietic stem-cell transplantation, EBV reactivation coincided with elevated MHC-I-restricted EBV-specific TRB sequence matches. Therapy with ocrelizumab, teriflunomide or dimethyl fumarate reduced EBV-specific, but not CMV-specific MHC-I-restricted TRB sequence matches. Together, this data suggests that the aberrant MHC-I-restricted T-cell response directed against EBV is specific to MS with regard to NMO, MOGAD and Susac's Syndrome and that it is specifically modified by MS treatments interfering with EBV host cells or activated lymphocytes.

Gamma Knife radiosurgery for multiple sclerosis-associated trigeminal neuralgia

BackgroundGamma Knife radiosurgery (GKRS) has well-known efficacy in the treatment of idiopathic trigeminal neuralgia (TN). However, few studies have evaluated the effects of GKRS in the treatment of multiple sclerosis (MS)-related TN. This study analyzed the efficacy and complications of GKRS for MS-related TN. MethodsThis retrospective study included 28 MS-related TN patients who underwent GKRS with a median follow-up of 27 (range, 12–181) months. The cisternal segment of the trigeminal nerve was targeted with a median radiation dose of 80 (80–90) Gy. Pain intensity was assessed using Barrow Neurological Institute (BNI)-Pain Intensity Scores (BNI-PIS). Before GKRS, all patients suffered from BNI pain levels of 4 or 5. A reduction in pain to BNI 3b or below was deemed as adequate pain relief. ResultsThe initial proportion of patients who experienced adequate pain relief was 71.4%, with a median interval of 21 (1–45) days. At the final follow-up, 50% of patients had achieved adequate pain relief. Ten patients (35.7%) suffered from complications, including four with facial sensorial dysfunctions, four with a decline in their corneal reflexes, and two with jaw weakness. Among the 20 initial responders, six (30%) patients suffered pain recurrence after a median interval of 35 (12–180) months. ConclusionsGKRS is an effective means of pain relief in MS-related TN, but has side effects that are relevant to other ablative treatments. The benefits and risks of GKRS should be discussed with patients who wish to avoid surgery or when previous treatments fail.

ENTIMOS: Decision Support Tool Highlights Potential Impact of Non-intravenous Therapies for Multiple Sclerosis on Patient Care via Clinical Scenario Simulation.

Administration of intravenous (IV), high-efficacy treatments (HETs) for the treatment of multiple sclerosis (MS) poses a high resourcing and planning burden on infusion centres, resulting in treatment delays that may increase the risk of breakthrough disease activity. Simulation tools can be used to systematically analyse capacity scenarios and identify and better understand constraints, therefore enabling decision-makers to optimise patient care. We have previously applied ENTIMOS, a discrete event simulation model, to assess scenarios of patient flow and care delivery using real-life data inputs from the neurology infusion suite at Charing Cross Hospital London. The model predicted that, given current capacity and projected demand, patients would experience high-risk treatment delays within 30 months. This study aimed to address key healthcare challenges for MS patient care management as seen from a neurologist's perspective. We used ENTIMOS to predict the impact of several distinct and clinically plausible scenarios on patient waiting times at the same MS infusion suite and to quantify mitigation strategies needed to assure continuity of care. We used real-world experience of an expert neurologist to identify five clinical scenarios: (1) switching patients to a subcutaneous (SC) MS treatment of the same therapeutic agent, in the same hospital setting; (2) extending opening times to the weekend; (3) reducing the number of infusion chairs (to simulate social distancing measures applied during the coronavirus disease 2019 [COVID-19] pandemic); (4) increasing demand for infusions; and (5) increasing the scheduling approval time. Patient waiting time for next due infusion and time to high-risk treatment delays (≥ 30 days) were the main analysed model outputs. Previously published base case results were used as reference. All hypothetical scenarios were run over a 3-year horizon (with the exception of scenario 1, which was run over a 3- and 5-year horizon). Strategies to mitigate treatment delays were analysed and discussed. Switching 50% of patients to SC treatment of the same therapeutic agent administered in hospital postponed the predicted high-risk treatment delays to shortly beyond the 3-year simulation timeframe (month 38). Weekend opening reduced waiting times from 20 days to 4 days and prevented treatment delays, however, at elevated labour costs. Reducing the infusion chairs increased waiting time to 53 days on average and 86 days at the end of the simulation, leading to high-risk treatment delays within 6 months. An increased demand for infusions increased waiting time to 26 days on average and 47 days at the end of the simulation, leading to high-risk treatment delays within 22 months. Prolonged scheduling approval time did not reduce the waiting time, nor postpone the high-risk treatment delays. Decision makers need transparency on capacity constraints to better plan resourcing at infusion suites and MS treatments. Our results showed that various mitigation measures, such as increasing capacity by additional infusion chairs per year and transferring patients to other infusion suites, may help prevent treatment delays. Switching patients from IV to an SC version of the same therapeutic agent reduced the waiting time moderately and postponed high-risk treatment delays. It was insufficient to prevent high-risk treatment delays in the long term.

Describing and Evaluating the Clinical Pharmacist's Role in a Canadian Multiple Sclerosis Clinic.

The current approach to treatment of multiple sclerosis (MS) involves use of disease-modifying therapies to slow progression of the disease, as well as the symptomatic management of fixed neurological deficits. Although pharmacists are uniquely positioned to support MS care teams with all aspects of medication management, their presence is rare among MS ambulatory care teams in Canada. To document the pharmacist's contributions and to evaluate the impact of the pharmacist's role following creation of a clinical pharmacist position in a Canadian MS clinic within a large, urban, university-affiliated, tertiary care centre. This study was conducted in 2 parts: a prospective, descriptive case study of the clinical pharmacist's role and a retrospective assessment of medication-related patient calls before and after implementation of the pharmacist position. The pharmacist performed a variety of clinical activities, with the greatest proportions of time spent on patient care (63.3%), drug access research (15.7%), and development and review of internal documents (9.0%). Patient care primarily involved conducting patient assessments, making medication recommendations, and assisting patients with medication-related issues. The proportion of medication-related issues resolved remained similar at 92.9% before and 95.7% after implementation of the clinical pharmacist (p = 0.48). The median time to resolve medication-related issues was reduced from 4.1 to 2.9 days (p = 0.016) with pharmacist involvement. Pharmacists can support MS care teams through a variety of medication-related clinical activities aligned with their scope and expertise. The presence of a pharmacist on the MS care team significantly reduced turnaround times for resolving medication-related issues, improving the efficiency and timeliness of care.

Transplantation of human umbilical cord mesenchymal stem cells optimized with IFN-γ is a potential procedure for modification of motor impairment in multiple sclerosis cases: a preclinical systematic review and meta-analysis study.

Stem cells transplantation (SCT) is known as a newfound strategy for multiple sclerosis (MS) treatment. Human umbilical cord mesenchymal stem cells (hUCMSCs) contain various regenerative features. Experimental autoimmune encephalomyelitis (EAE) is a laboratory model of MS. This meta-analysis study was conducted to assess the overall therapeutic effects of hUCMSCs on reduction of clinical score (CS) and restoration of active movement in EAE-induced animals. For comprehensive searching (in various English and Persian databases until May 1, 2024), the main keywords of "Experimental Autoimmune Encephalomyelitis", "Multiple Sclerosis", "Human", "Umbilical Cord", "Mesenchymal", and "Stem Cell" were hired. Collected data were transferred to the citation manager software (EndNote x8) and duplicate papers were merged. Primary and secondary screenings were applied (according to the inclusion and exclusion criteria) and eligible studies were prepared for data collection. CS of two phases of peak and recovery of EAE were extracted as the difference in means and various analyses including heterogeneity, publication bias, funnel plot, and sensitivity index were reported. Meta-analysis was applied by CMA software (v.2), P<0.05 was considered a significant level, and the confidence interval (CI) was determined 95% (95% CI). Six eligible high-quality (approved by ARRIVE checklist) papers were gathered. The difference in means of peak and recovery phases were -0.775 (-1.325 to -0.225; P=0.006; I2=90.417%) and -1.230 (-1.759 to -0.700; P<0.001; I2=93.402%), respectively. The overall therapeutic effects of SCT of hUCMSCs on the EAE cases was -1.011 (95% CI=-1.392 to -0.629; P=0.001). hUCMSCs transplantation through the intravenous route to the animal MS model (EAE) seems a considerably effective procedure for the alleviation of motor defects in both phases of peak and recovery.

Advancing understanding of the role of IL-22 in myelination: insights from the Cuprizone mouse model.

Despite significant advancements in the field, the pathophysiology of multiple sclerosis (MS) remains partially understood, with limited therapeutic options available for this debilitating condition. The precise impact of Interleukin-22 (IL-22) in the context of MS is still incompletely elucidated with some evidence suggesting its protective role. To provide a more comprehensive understanding of the role of IL-22, we investigated its effect on remyelination in a mouse model of demyelination induced by Cuprizone. Mice underwent a 6 week regimen of Cuprizone or vehicle, followed or not by intraperitoneal administration of IL-22. Behavioral assessments including tail suspension and inverted screen tests were conducted, alongside histological, histochemical, and quantitative PCR analyses. In Cuprizone-treated mice, IL-22 significantly improved motor and behavioral performance and robustly promoted remyelination in the corpus callosum. Additionally, IL-22 administration led to a significant elevation in MBP transcription in brain biopsies of treated mice. These findings collectively suggest a crucial role for IL-22 in the pathophysiology of MS, particularly in supporting the process of remyelination. These results offer potential avenues for expanding therapeutic strategies for MS treatment. Ongoing experiments aim to further unravel the underlying mechanisms of IL-22 action.

Effective Application of Biocompatible Magnetite Nanoparticles in the Treatment of Multiple Sclerosis: Results of a Clinical Study

Multiple sclerosis (MS) is a serious neurological disorder due to its widespread prevalence, chronic nature, frequent progression to disability, and tendency to affect young people. The pathogenesis of MS is based on the immunopathogenesis hypothesis. Biocompatible magnetite nanoparticles, which exhibit selective sorption activity towards cell membrane surface proteins, circulating immune com-plexes, lymphocytotoxic antibodies, and the complement system, as well as enhance phagocytic ac-tivity and the completion index of leukocyte phagocytosis, can be effectively used for immunocor-rection. The main goal of the study is to slow the progression of MS, improve the neurological status and overall condition of the patient, and reduce the dynamics of the spread of demyelinating lesions in the brain. Materials and methods: A patient diagnosed with multiple sclerosis, secondary progres-sive type, cerebrospinal form, at the clinical aggravation stage was included in the study. Neurologi-cal status and disability were assessed using the EDSS scale, and brain MRI with contrast enhance-ment was performed. The nanodevice Micromage-B was administered orally as an immunosorbent and immunomodulator. The regimen and dosage of Micromage-B were personalized. Assessments of general condition and neurological status were conducted every 7 days for 6 months, with contrast-enhanced brain MRI performed in the 5th month. Results: The use of Micromage-B in MS treatment led to an objective improvement in neurological status, with reduced stiffness and fatigue in the lower extremities. Gait and coordination improved, hand tremors decreased, depression and concen-tration disorders subsided, appetite was restored, and speech improved. Throughout the treatment period, positive dynamics in the normalization of neurological status were observed. After 6 months, the total score on the EDSS scale decreased from 210 to 45. The most significant improvements were observed in the evaluation of the pyramidal system and coordination, with the EDSS Disability Scale score decreasing from 6.0 to 5.0. For the first time, contrast-enhanced brain MRI showed a reduction in the number of new demyelination foci by the 4th month of Micromage-B administra-tion. The positive changes in neurological status correlated with the MRI results. The recovery of central nervous system activity in MS is likely not only due to the immunosuppressive properties of magnetite nanoparticles but also due to the activation of remyelination mechanisms and oligoden-drocyte differentiation through enzymatic methylation. Conclusion: The use of biocompatible nanodevices in the complex treatment of MS is promising. Further improvement and study of the regimen and method of using biocompatible magnetite nanoparticles to enhance MS treatment effec-tiveness are required.

Discovery of Potent, Orally Bioavailable Sphingosine-1-Phosphate Transporter (Spns2) Inhibitors.

Targeting the S1P pathway has resulted in the development of S1P1 receptor modulators for the treatment of multiple sclerosis and ulcerative colitis. We hypothesize that targeting an upstream node of the S1P pathway may provide an improved adverse event profile. In this report, we performed a structure-activity relationship study focusing on the benzoxazole scaffold in SLB1122168, which lead to the discovery of 11i (SLF80821178) as a potent inhibitor of S1P release from HeLa cells (IC50: 51 ± 3 nM). Administration of SLF80821178 to mice induced ∼50% reduction in circulating lymphocyte counts, recapitulating the lymphopenia characteristic of Spns2 null animals. Molecular modeling studies suggest that SLF80821178 binds Spns2 in its occluded inward-facing state and forms hydrogen bonds with Asn112 and Ser211 and π stacking with Phe234. Taken together, SLF80821178 can serve as a scaffold for future inhibitor development and represents a chemical tool to study the therapeutic implication of inhibiting Spns2.

Mesenchymal stem cells and their derived exosomes in multiple sclerosis disease: from paper to practice.

Multiple sclerosis (MS) is a chronic neurodegenerative, inflammatory, and demyelinating disease of the central nervous system (CNS). Current medicines are not sufficient to control the inflammation and progressive damage to the CNS that is known in MS. These drawbacks highlight the need for novel treatment options. Cell therapy can now be used to treat complex diseases when conventional therapies are ineffective. Mesenchymal stem cells (MSCs) are a diverse group of multipotential non-hematopoietic stromal cells which have immunomodulatory, neurogenesis, and remyelinating capacity. Their advantageous effects mainly rely on paracrine, cell-cell communication and differentiation properties which introduced them as excellent candidates for MS therapy. Exosomes, as one of the MSCs secretomes, have unique properties that make them highly promising candidates for innovative approach in regenerative medicine. This review discusses the therapeutic potential of MSCs and their derived exosomes as a novel treatment for MS, highlighting the differences between these two approaches.

Evaluating the Therapeutic Potential of Ublituximab in the Treatment of MS: Design, Development and Place in Therapy.

B cells are critical to the pathogenesis of multiple sclerosis (MS), an autoimmune disease of the central nervous system. B cell depletion using anti-CD20 monoclonal antibodies (mAbs) has proven to be an extremely successful treatment strategy, with profound suppression of both clinical and radiological evidence of focal inflammatory disease. Several anti-CD20 mAbs are now licensed for use in MS, with ublituximab being the latest to gain regulatory approval. The unique properties of each of the anti-CD20 mAb may result in nuanced differences in timing, duration and depth of B cell depletion, with the potential for such differences to have a clinical relevance to both drug efficacy and adverse effects. In this review, we summarize the design, development, and current place in MS therapy for ublituximab.

Enduring metabolic modulation in the cardiac tissue of elderly CD-1 mice two months post mitoxantrone treatment

Mitoxantrone (MTX) is a therapeutic agent used in the treatment of solid tumors and multiple sclerosis, recognized for its cardiotoxicity, with underlying molecular mechanisms not fully disclosed. The cardiotoxicity is influenced by risk factors, including age. Our study intended to assess the molecular effect of MTX on the cardiac muscle of old male CD-1 mice. Mice aged 19 months received a total cumulative dose of 4.5 mg/kg of MTX (MTX group) or saline solution (CTRL group). Two months post treatment, blood was collected, animals sacrificed, and the heart removed. MTX caused structural cardiac changes, which were accompanied by extracellular matrix remodeling, as indicated by the increased ratio between matrix metallopeptidase 2 and metalloproteinase inhibitor 2. At the metabolic level, decreased glycerol levels were found, together with a trend towards increased content of the electron transfer flavoprotein dehydrogenase. In contrast, lower glycolysis, given by the decreased content of glucose transporter GLUT4 and phosphofructokinase, seemed to occur. The findings suggest higher reliance on fatty acids oxidation, despite no major remodeling occurring at the mitochondrial level. Furthermore, the levels of glutamine and other amino acids (although to a lesser extent) were decreased, which aligns with decreased content of the E3 ubiquitin-protein ligase Atrogin-1, suggesting a decrease in proteolysis. As far as we know, this was the first study made in old mice with a clinically relevant dose of MTX, evaluating its long-term cardiac effects. Even two months after MTX exposure, changes in metabolic fingerprint occurred, highlighting enduring cardiac effects that may require clinical vigilance.

Budget impact analysis of biosimilar natalizumab in the US.

Biosimilars provide an opportunity for a more sustainable and cost-effective treatment for multiple sclerosis (MS). This study evaluated the potential financial impact of implementing a formulary change from reference to biosimilar natalizumab (NTZ) from the US commercial payer perspective. The budget impact of transitioning to biosimilar NTZ for the treatment of relapsing-remitting MS (RRMS) was estimated over a 3-year time horizon based on real-world dosing. Additional scenario analyses were conducted by varying the price differential of biosimilar NTZ. The target population was estimated from a 1-million-member hypothetical commercial health plan. Model inputs were drug acquisition costs and treatment-related and patient coinsurance costs. Budget impact and cost savings per member per year were calculated by assuming a biosimilar uptake of 10% in year 1 to 20% in year 3. Over 3 years, 255 patients were estimated to be treated with high-efficacy disease-modifying therapies for RRMS. The inclusion of biosimilar NTZ onto a formulary would result in cumulative cost savings to payers of $452,611 over 3 years, with mean savings per treated member per year of $1179, $1769, and $2359 in years 1, 2, and 3, respectively. One-way sensitivity analyses indicated that budget impact results were most sensitive to drug acquisition costs of both reference and biosimilar NTZ. Adoption of biosimilar NTZ can yield considerable cost savings to US health plans that could result in increased treatment access for patients with RRMS.

Neuroinflammation-on-a-chip for multiple sclerosis research: a narrative review.

Multiple sclerosis (MS) is a chronic inflammatory condition that impacts the central nervous system. It is distinguished by processes like demyelination, gliosis, neuro-axonal harm, and inflammation. The prevailing theory suggests that MS originates from an immune response directed against the body's own antigens within the central nervous system. The main aim of this research paper "Neuroinflammation-on-a-Chip" for studying multiple sclerosis is to enhance our comprehension of MS development, demonstrate the application of cutting-edge technology, and potentially provide valuable insights for therapeutic approaches. The available literature for this Narrative Review was searched on various bibliographic databases, PubMed, NCBI, and many other medical references using an individually verified, prespecified approach. Studies regarding the significance of MS and its neuroinflammatory pathogenesis in addition to the development and optimization of neuroinflammatory-on-a-chip and the advancement in innovations in this field have been reviewed in this research for a better understanding of "Neuroinflammation-on-a-chip for multiple sclerosis". The level of evidence of the included studies was considered as per the Centre for Evidence-Based Medicine recommendations. Several studies have indicated that the brain-chip model closely mimics cortical brain tissue compared to commonly used conventional cell culture methods like the Transwell culture system. Additionally, these studies have clearly demonstrated that further research using brain chips has the potential to enhance our understanding of the molecular mechanisms and roles of blood-brain barrier (BBB) transporters in both normal and disease conditions. Understanding neuroinflammation processes remains essential to establish new MS treatments approaches. The utilization of brain chips promises to advance our understanding of the molecular processes involving BBB transporters, both in normal and diseased states. Further research needs to be addressed in order to enhance the performance and understanding of neuroinflammation on a chip, hence aiming to provide more effective treatments for all CNS diseases.

Assessment of ocrelizumab impact on neurofilament levels in multiple sclerosis patients

Abstract Background Multiple sclerosis (MS) is a debilitating neurological disease characterized by inflammation, demyelination, and neurodegeneration in the central nervous system. Despite extensive research, the pathology of MS remains incompletely understood. Ocrelizumab (OCRE), a monoclonal antibody targeting CD20-positive B cells, has shown efficacy in relapsing (RR) and primary progressive (PP) MS. Neurofilaments (Nf) are emerging biomarkers of neuroaxonal injury, reflecting disease activity and treatment response in MS. This study aimed to assess the impact of OCRE on serum Nf levels (NfLs) in RRMS and PPMS patients and explore factors influencing treatment response. Methods A prospective study included 23 RRMS and PPMS patients initiating OCRE and 23 healthy controls. Serum NfLs were quantified using ELISA. Statistical analyses evaluated changes in NfLs and factors influencing treatment response. Results MS patients exhibited significantly higher NfLs than controls. OCRE treatment led to a significant reduction in NfLs after one cycle. Age and gender influenced treatment response, with older patients and females experiencing greater NfL reduction. Disability level and disease duration did not significantly affect NfLs reduction. Both RRMS and PPMS patients showed decreased NfLs levels with OCRE treatment. Conclusions In conclusion, OCRE demonstrated efficacy in reducing NfLs levels in RRMS and PPMS patients after one cycle, with potential age and gender-related variations in treatment response. Larger longitudinal studies are needed to further elucidate OCRE’s mechanisms and implications for personalized MS treatment.

UNLOCKING HOPE: OVERCOMING THERAPEUTIC CHALLENGES IN PROGRESSIVE MULTIPLE SCLEROSIS

Progressive forms of multiple sclerosis (MS) present significant therapeutic challenges, underscoring the pressing need for effective treatments in this domain. While relapsing-remitting MS (RRMS) transitions to secondary progressive MS (SPMS) for many patients, others experience primary progressive MS (PPMS) from the diseases onset. Despite similarities in pathophysiology and clinical progression between SPMS and PPMS, treatment options remain limited. The recent approval of ocrelizumab for PPMS marks a notable advancement, though its efficacy is modest. This retrospective study, conducted at the Neurology Department of Mohammed VI University Hospital, evaluates the tolerance and therapeutic efficacy of various treatments in progressive MS. Nineteen patient records spanning six years were analyzed, with therapeutic interventions including Fingolimod, Rituximab, cyclophosphamide-solumedrol, and ocrelizumab. Assessments utilizing the Expanded Disability Status Scale (EDSS) revealed stabilization or improvement in 15.7% of secondary progressive MS and 21% of primary progressive MS patients after 12 months of treatment. The duration of the progressive phase emerged as a key predictor of therapeutic response. Despite the approval of ocrelizumab in Morocco for PPMS, its utilization remains limited, suggesting the need for targeted studies focusing on early-stage clinical progression. Overall, this study underscores the unmet need for effective treatments in progressive MS and highlights ongoing research efforts aimed at addressing this challenge.