Neurotransmitter systems in the etiology of major neurological disorders: Emerging insights and therapeutic implications

Ageing Research Reviews, Год журнала: 2023, Номер 89, С. 101994 - 101994

Опубликована: Июнь 28, 2023

Язык: Английский

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Tolebrutinib versus Teriflunomide in Relapsing Multiple Sclerosis

New England Journal of Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Tolebrutinib is an oral, brain-penetrant, and bioactive Bruton's tyrosine kinase inhibitor that modulates peripheral inflammation persistent immune activation within the central nervous system, including disease-associated microglia B cells. More data are needed on its efficacy safety in treating relapsing multiple sclerosis. In two phase 3, double-blind, double-dummy, event-driven trials (GEMINI 1 GEMINI 2), participants with sclerosis were randomly assigned a 1:1 ratio to receive tolebrutinib (60 mg once daily) or teriflunomide (14 daily), each matching placebo. The primary end point was annualized relapse rate. key secondary confirmed worsening of disability sustained for at least 6 months, which assessed time-to-event analysis pooled across trials. A total 974 enrolled 1, 899 2. median follow-up 139 weeks. rate groups 0.13 0.12, respectively, (rate ratio, 1.06; 95% confidence interval [CI], 0.81 1.39; P = 0.67) 0.11 0.11, 2 1.00; CI, 0.75 1.32; 0.98). percentage months 8.3% 11.3% (hazard 0.71; 0.53 0.95; no formal hypothesis testing conducted owing prespecified hierarchical plan, width not adjusted testing). who had adverse events similar treatment groups, although minor bleeding higher group than (petechiae occurred 4.5% vs. 0.3%, heavy menses 2.6% 1.0%). superior decreasing rates among (Funded by Sanofi; ClinicalTrials.gov numbers, NCT04410978 NCT04410991, respectively.).

Язык: Английский

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Sex and Gender Differences in Neurodegenerative Diseases: Challenges for Therapeutic Opportunities

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6354 - 6354

Опубликована: Март 28, 2023

The term "neurodegenerative diseases" (NDs) identifies a group of heterogeneous diseases characterized by progressive loss selectively vulnerable populations neurons, which progressively deteriorates over time, leading to neuronal dysfunction. Protein aggregation and have been considered the most characteristic hallmarks NDs, but growing evidence confirms that significant dysregulation innate immune pathways plays crucial role as well. NDs vary from multiple sclerosis, in autoimmune inflammatory component is predominant, more "classical" such Parkinson's disease, Alzheimer's amyotrophic lateral spinal muscular atrophy. Of interest, many clinical differences reported seem be closely linked sex, may justified changes mechanisms between affected females males. In this review, we examined some studied looking at their pathogenic phenotypical features highlight sex-related discrepancies, if any, with particular interest individuals' responses treatment. We believe pointing out these practice help achieve successful precision personalized care.

Язык: Английский

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Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders

Molecular Neurobiology, Год журнала: 2023, Номер 60(11), С. 6476 - 6529

Опубликована: Июль 17, 2023

Язык: Английский

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Immune System Dysregulation in the Progression of Multiple Sclerosis: Molecular Insights and Therapeutic Implications

Neuroscience, Год журнала: 2024, Номер 548, С. 9 - 26

Опубликована: Апрель 30, 2024

Язык: Английский

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Serum biomarkers at disease onset for personalized therapy in multiple sclerosis

Brain, Год журнала: 2024, Номер unknown

Опубликована: Авг. 5, 2024

Abstract The potential for combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict worsening disability in multiple sclerosis remains underexplored. We aimed investigate whether sNfL sGFAP values identify distinct subgroups of patients according the risk their response disease-modifying treatments (DMTs). This multicentre study, conducted across 13 European hospitals, spanned from 15 July 1994 18 August 2022, with follow-up until 26 September 2023. enrolled who had samples collected within 12 months disease onset before initiating DMTs. Multivariable regression models were used estimate relapse-associated (RAW), progression independent relapse activity (PIRA) Expanded Disability Status Scale (EDSS) score 3. Of 725 included, median age was 34.2 (interquartile range, 27.6–42.4) years, 509 (70.2%) female. duration 6.43 4.65–9.81) years. Higher associated an elevated RAW [hazard ratio (HR) 1.45; 95% confidence interval (CI) 1.19–1.76; P < 0.001], PIRA (HR 1.43; CI 1.13–1.81; = 0.003) reaching EDSS 3 1.55; 1.29–1.85; 0.001). Moreover, higher linked a achieving 1.36; 1.06–1.74; 0.02) and, low values, 1.86; 1.01–3.45; 0.04). also examined combined effect levels. Patients exhibited all outcomes served as reference. Untreated high showed RAW, Injectable or oral DMTs reduced these but failed mitigate Conversely, high-efficacy counteracted heightened outcomes, except increased 3, which remained unchanged either other In conclusion, evaluating at might phenotypes diverse immunological pathways acquisition therapeutic response.

Язык: Английский

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Effect of Different Treatments on Retinal Thickness Changes in Patients With Multiple Sclerosis: A Review

CNS Neuroscience & Therapeutics, Год журнала: 2025, Номер 31(1)

Опубликована: Янв. 1, 2025

ABSTRACT Background Multiple sclerosis (MS) is an autoimmune disorder affecting the central nervous system, with varying clinical manifestations such as optic neuritis, sensory disturbances, and brainstem syndromes. Disease progression monitored through methods like MRI scans, disability scales, optical coherence tomography (OCT), which can detect retinal thinning, even in absence of neuritis. MS involves neurodegeneration, particularly trans‐synaptic degeneration, extends beyond initial injury site. This review focuses on impact different treatments thickness assessed by OCT. Results Injectable drugs, interferon beta glatiramer acetate (GA), have a relatively modest atrophy. Oral medications Fingolimod, Teriflunomide, Dimethyl fumarate also impacts thickness. Fingolimod has been shown to protect against thinning but may lead macular edema. DMF‐treated patients had less ganglion cell–inner plexiform layer than GA‐treated more compared natalizumab‐treated healthy controls. Teriflunomide's layers remains unexplored human studies. Monoclonal antibodies, including Alemtuzumab, Rituximab, Ocrelizumab, Natalizumab, protective effects Alemtuzumab‐treated showed significantly atrophy interferon‐ patients. Rituximab initially increased rates first months subsequently demonstrated potential neuroprotective effects. Ocrelizumab slowed rate inner nuclear progressive forms disease. Natalizumab considered most effective reducing atrophy, peripapillary nerve fiber layer. Conclusions It's important note that effectiveness these vary depending subtype individual factors. Future research should explore long‐term their correlations overall disease

Язык: Английский

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Towards a biological view of multiple sclerosis from early subtle to clinical progression: an expert opinion

Journal of Neurology, Год журнала: 2025, Номер 272(2)

Опубликована: Фев. 1, 2025

Язык: Английский

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Cloud and IoT based Smart Agent-driven Simulation of Human Gait for Detecting Muscles Disorder

Heliyon, Год журнала: 2025, Номер 11(2), С. e42119 - e42119

Опубликована: Янв. 1, 2025

Motion disorders affect a significant portion of the global population. While some symptoms can be managed with medications, these treatments often impact all muscles uniformly, not just affected ones, leading to potential side effects including involuntary movements, confusion, and decreased short-term memory. Currently, there is no dedicated application for differentiating healthy from abnormal ones. Existing analysis applications, designed other purposes, lack essential software engineering features such as user-friendly interface, infrastructure independence, usability learning ability, cloud computing capabilities, AI-based assistance. This research proposes computer-based methodology analyze human motion differentiate between unhealthy muscles. First, an IoT-based approach proposed digitize using smartphones instead hardly accessible wearable sensors markers. The data then simulated neuromusculoskeletal system. An agent-driven modeling method ensures naturalness, accuracy, interpretability simulation, incorporating neuromuscular details Henneman's size principle, action potentials, motor units, biomechanical principles. results are provided medical clinical experts aid in further investigation. Additionally, deep learning-based ensemble framework assist simulation results, offering both accuracy interpretability. A graphical interface enhances application's usability. Being fully cloud-based, infrastructure-independent accessed on smartphones, PCs, devices without installation. strategy only addresses current challenges treating but also paves way simulations by considering scientific computational requirements.

Язык: Английский

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Therapeutic potential of Pranlukast against cuprizone-induced inflammatory demyelination and sensory impairment in mice: comparison with Fingolimod.

NeuroToxicology, Год журнала: 2025, Номер 107, С. 37 - 52

Опубликована: Янв. 31, 2025

Язык: Английский

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