Therapeutic Advances in Neurological Disorders最新文献

{"title":"Patterns and predictors of therapeutic response to efgartigimod in acetylcholine receptor-antibody generalized myasthenia gravis subtypes.","authors":"Lei Jin, Zhangyu Zou, Qinzhou Wang, Wenshuang Zeng, Qilong Jiang, Jing Chen, Jianquan Shi, Yanyan Yu, Daojun Hong, Quantao Zeng, Song Tan, Yaoxian Yue, Zhouao Zhang, Yong Zhang, Xiuming Guo, Lei Du, Zhongyan Zhao, Shixiong Huang, Ying Chen, Zongtai Wu, Chong Yan, Jianying Xi, Jie Song, Sushan Luo, Chongbo Zhao","doi":"10.1177/17562864251319656","DOIUrl":"10.1177/17562864251319656","url":null,"abstract":"<p><strong>Background: </strong>Efgartigimod is an approved biologic for generalized myasthenia gravis (gMG), which is an autoimmune disease and can potentially be life-threatening. However, the therapeutic response to efgartigimod among the acetylcholine receptor gMG (AChR-gMG) subtypes remains inconclusive.</p><p><strong>Objective: </strong>To explore the patterns and predictors for the therapeutic response to efgartigimod among AChR-gMG subtypes.</p><p><strong>Design: </strong>This prospective, observational study included AChR-gMG patients treated with efgartigimod at 15 centers in China with a follow-up for at least 20 weeks.</p><p><strong>Methods: </strong>The primary outcome was the proportion of minimal symptom expression (MSE) responders, denoted by a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 0 or 1 within 4 weeks and maintained for ⩾4 weeks. AChR antibody-positive MG (AChR-MG) subtypes were classified into early onset myasthenia gravis (EOMG), late-onset myasthenia gravis (LOMG), and thymoma-associated myasthenia gravis (TAMG). The predictive factors for MSE responders were identified by univariate and multivariate logistic regression analysis.</p><p><strong>Results: </strong>One hundred sixteen patients were included with a median follow-up duration of 238 days (172.5-306.3). There were 50 (43.1%) patients with EOMG, 28 (24.1%) with LOMG and 38 (32.8%) with TAMG. After efgartigimod initiation, 35 (30.2%) patients were MSE responders, and the proportion of MSE responders was highest in the LOMG group (42.9%). The MG-ADL score reduction in the LOMG group was more significant than in the EOMG group by weeks 16 and 20 (both <i>p</i> = 0.022). Response patterns to efgartigimod among the AChR-MG subtypes differed as measured by the proportion of improved patients and MSE. LOMG presented sustained symptom control, while EOMG and TAMG showed more fluctuations. Eight TAMG patients (21.1%) switched to another biologic (<i>p</i> = 0.005). Baseline MG-ADL was an independent predictor for therapeutic response to efgartigimod (<i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Our findings revealed patterns of treatment responses among AChR-gMG subtypes, with LOMG patients potentially presenting a more sustained response. These findings likely provide preliminary data for precision therapy in MG in the era of biologics.</p><p><strong>Trial registration: </strong>NCT04535843.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251319656"},"PeriodicalIF":4.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of educational attainment on diagnostic and treatment delays in multiple sclerosis: a nationwide cohort study in Denmark.","authors":"Elisabeth Framke, Melinda Magyari","doi":"10.1177/17562864251313918","DOIUrl":"10.1177/17562864251313918","url":null,"abstract":"<p><strong>Background: </strong>In multiple sclerosis (MS), the educational gradient in diagnostic and disease-modifying treatment (DMT) delays is sparsely examined, and the results are mixed.</p><p><strong>Objectives: </strong>Among patients with relapsing-remitting MS (RRMS), we aimed to examine the educational gradient in diagnostic delay and delay in the initiation of the first DMT.</p><p><strong>Design: </strong>A nationwide cohort study.</p><p><strong>Methods: </strong>We linked the Danish Multiple Sclerosis Registry with other nationwide registries. Diagnostic delay was evaluated in 4344 patients ⩾20 years at clinical onset with clinical onset from January 1, 2012, onwards, diagnosed by March 1, 2023. DMT delay was evaluated in 5402 patients ⩾20 years at MS diagnosis who were diagnosed from January 1, 2012, to March 1, 2022, with DMT initiation follow-up until March 1, 2023. The highest completed education before onset and diagnosis, respectively, was categorized using the International Standard Classification of Education (ISCED) into low (ISCED 0-2), medium (ISCED 3-4) and high (ISCED ⩾5) education. Endpoints were categorized according to their duration into four groups based on a population-specific quartile split. The highest quartile comprised long duration (⩾500 days (diagnostic delay) and ⩾76 days (DMT delay)). We calculated crude and adjusted odds ratios (OR) with 95% confidence intervals (CI).</p><p><strong>Results: </strong>The mean age was 36.7 years (SD = 10.3, diagnostic delay population) and 39.2 years (SD = 10.9, DMT delay population). Most were female (67.4% and 68.3%) and of Danish origin (90.3% and 90.5%). Patients with low educational attainment did not have higher odds of diagnostic delay (OR = 1.05; 95% CI: 0.81-1.35) but had higher odds of DMT delay (OR = 1.48; 95% CI: 1.17-1.87) compared to patients with high educational attainment.</p><p><strong>Conclusion: </strong>In adult patients with RRMS, low educational attainment was associated with higher odds of DMT delay but not diagnostic delay. Targeted interventions are needed to address educational disparities in healthcare access and treatment initiation.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251313918"},"PeriodicalIF":4.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11826836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term efficacy and safety of alemtuzumab in participants with highly active MS: TOPAZ clinical trial and interim analysis of TREAT-MS real-world study.","authors":"Tjalf Ziemssen, Ann D Bass, Bart Van Wijmeersch, Sara Eichau, Stephan Richter, Frank Hoffmann, Nicole M Armstrong, Magdalena Chirieac, Janete Cunha-Santos, Barry A Singer","doi":"10.1177/17562864241306575","DOIUrl":"10.1177/17562864241306575","url":null,"abstract":"<p><strong>Background: </strong>Alemtuzumab is a disease-modifying therapy for highly active relapsing-remitting multiple sclerosis (RRMS). Sustained efficacy up to 9 years was observed in the phase IIIb/IV open-label TOPAZ clinical trial and assessed in the real-world retrospective and prospective study, TREAT-MS.</p><p><strong>Objectives: </strong>To examine long-term efficacy and safety of alemtuzumab in participants with multiple sclerosis (MS) and highly active disease (HAD) by combining up to 13 years of TOPAZ data and TREAT-MS interim data.</p><p><strong>Design: </strong>TOPAZ: Randomized participants completing core CARE-MS I and II could receive additional alemtuzumab (12 mg/day, 3 consecutive days; ⩾12 months apart) for 11-13 years after initiating treatment. TREAT-MS: Participants from German MS clinics were observed for 4 years after last alemtuzumab treatment phase.</p><p><strong>Methods: </strong>Efficacy outcomes (annualized relapse rate (ARR), change in Expanded Disability Status Scale (EDSS), 6-month confirmed disability worsening/improvement, magnetic resonance imaging), and adverse events (AEs) were examined. Primary HAD definition (⩾2 relapses in the year prior to baseline and ⩾1 gadolinium-enhancing lesion at baseline), and two alternative HAD definitions were assessed.</p><p><strong>Results: </strong>More participants from CARE-MS I (28%) and II (24%) met primary HAD criteria than TREAT-MS (~14%). Mean ARR for alemtuzumab-treated HAD participants was significantly reduced in CARE-MS I and II (0.14 and 0.15, respectively, Years 3-13) and in TREAT-MS (0.24, <b>></b>2 years). Stable/improved EDSS scores were achieved by 74% of HAD participants in CARE-MS I, 67% in CARE-MS II (both Year 11), and 79% in TREAT-MS (Year 3.6), with 6-month CDI achieved by about half at Year 11 (CARE-MS I, II). Annual treatment-emergent AE incidences declined in TOPAZ and were lower in TREAT-MS.</p><p><strong>Conclusion: </strong>Sustained efficacy of alemtuzumab was observed for clinical and radiological outcomes in participants with HAD in the TOPAZ clinical trial and real-world TREAT-MS study with no new safety signals.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (CARE-MS I, NCT00530348; CARE-MS II, NCT00548405; CARE-MS Extension Study, NCT00930553; TOPAZ, NCT02255656). Paul-Ehrlich-Institut (TREAT-MS, NIS 281).</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241306575"},"PeriodicalIF":4.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-induced dementia: a real-world pharmacovigilance study using the FDA Adverse Event Reporting System database.","authors":"Lisi Xu, Ruonan Zhang, Xiaolin Zhang, Xiuli Shang, Daifa Huang","doi":"10.1177/17562864251315137","DOIUrl":"https://doi.org/10.1177/17562864251315137","url":null,"abstract":"<p><strong>Background: </strong>Dementia is a serious adverse event (AE) that requires attention in clinical practice. However, information on drug-induced dementia is limited. The U.S. FDA Adverse Event Reporting System (FAERS) serves as an important resource for identifying real-world adverse drug reactions and safety signals.</p><p><strong>Objective: </strong>This study aimed to use FAERS data to identify drugs associated with increased dementia risk.</p><p><strong>Design: </strong>A secondary analysis of the FAERS database was conducted using disproportionality analysis methods.</p><p><strong>Methods: </strong>We reviewed dementia-related reports in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023, used the Medical Dictionary for Regulatory Activity to identify dementia cases and summarized the corresponding list of potential medications, counted the dementia-causing medication classes with the highest frequency of reports, and disaggregated all medications.</p><p><strong>Results: </strong>The study identified 31,881 dementia-related AEs in the FAERS database, with an increasing trend over time, particularly among females and individuals over 65. Apixaban had the most reports (1631). Disproportionality analyses revealed that rivastigmine, nicergoline, aducanumab, amlodipine/atorvastatin, and dihydroergometrine had the highest risk, based on reporting odds ratio, proportional reporting ratio, and information component. Only valproate and tramadol among the top 50 drugs included a potential dementia risk in their package inserts.</p><p><strong>Conclusion: </strong>This study identified a list of medications associated with dementia risk, many of which lack dementia warnings on their labels. Increased monitoring is necessary for high-risk individuals, and further research is required to clarify these associations and improve patient safety.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251315137"},"PeriodicalIF":4.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of cannabidiol as adjunctive therapy in adult patients with drug-resistant epilepsy: a systematic review and meta-analysis.","authors":"Marjorie Jia Yi Ong, Muhammad Samir Haziq Abd Rahman, Vanessa Lin Lin Lee, Kong Heng Lee, Carmen Jia Yinn Chang, Ching Soong Khoo, Rozita Hod, Hui Jan Tan, Eugen Trinka","doi":"10.1177/17562864251313914","DOIUrl":"https://doi.org/10.1177/17562864251313914","url":null,"abstract":"<p><strong>Background: </strong>Highly purified cannabidiol (CBD), recently approved for various neurological disorders, is explored as a potential therapeutic avenue for drug-resistant epilepsy (DRE) among adult people with epilepsy (PWE) in this systematic review and meta-analysis.</p><p><strong>Objectives: </strong>To conduct an extensive literature review and meta-analysis of CBD use for DRE in adult PWE.</p><p><strong>Design: </strong>Systematic review and meta-analysis.</p><p><strong>Data sources and methods: </strong>We conducted a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and two electronic resources; we searched Ovid MEDLINE and Scopus using appropriate keywords until August 2023. Data were presented as standardized mean difference (SMD) and odds ratio with confidence interval (CI) via random effect. We appraised the risk of bias of the included studies using the Joanna Briggs Institute critical appraisal tool while their strength of evidence with the Oxford Centre for Evidence-Based Medicine (OCEBM) and Grading of Recommendations Assessment Development and Education (GRADE) Levels of Evidence.</p><p><strong>Results: </strong>We identified 16 studies, 3 of which were randomized controlled trials and 3 prospective cohort studies, while the rest were expanded access programs, deriving a total of 668 participants receiving CBD for seizure control. CBD was used concomitantly with antiseizure medications in all studies. There was a statistically significant seizure reduction in the group receiving CBD therapy compared to the placebo group (SMD: -1.50, 95% CI (-3.47, 0.47), <i>p</i> < 0.01).</p><p><strong>Conclusion: </strong>The evidence on CBD use in adult patients with DRE demonstrates a moderate level of certainty according to GRADE level and OCEBM level 2. Further prospective studies involving multiple centers are encouraged to study both the efficacy and safety of CBD in adult patients with DRE.</p><p><strong>Trial registration: </strong>International Prospective Register of Systematic Reviews (PROSPERO) 2023 CRD42023449955.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251313914"},"PeriodicalIF":4.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-country cohort database study to assess pregnancy and infant outcomes after potential maternal or paternal exposure to cladribine tablets in the treatment of multiple sclerosis: the CLEAR study methods and status update.","authors":"Kerstin Hellwig, Melinda Magyari, Thomas M MacDonald, Carolyn E Cesta, Stig Wergeland, Maarit K Leinonen, Asher Ornoy, Sandra Vukusic, Alexandra Lauer, Xiaolei Zhou, Alison Kawai, Rachel Weinrib, Alejandro Arana, Tahani Boumenna","doi":"10.1177/17562864241310996","DOIUrl":"10.1177/17562864241310996","url":null,"abstract":"<p><strong>Background: </strong>Cladribine tablets are contraindicated during pregnancy; therefore, safety data on pregnancies exposed to this treatment are limited. CLEAR collects and describes pregnancy outcomes in this understudied population.</p><p><strong>Objectives: </strong>To describe the main features of the CLEAR study design, including the data sources and the methodological approach, and provide a status update.</p><p><strong>Design: </strong>CLEAR is a non-interventional, multi-database, comparative cohort study. Four cohorts are included: pregnancies of women with multiple sclerosis (MS) exposed to cladribine tablets (maternal cohort exposed); pregnancies of women with MS unexposed to any disease-modifying therapy (DMT; maternal cohort unexposed); pregnancies fathered by men with MS exposed to cladribine tablets; and pregnancies fathered by men with MS unexposed to any DMT.</p><p><strong>Methods: </strong>A staggered methodological approach, using data from Denmark, Finland, France, Germany, Norway, Scotland, and Sweden, will be applied to analyze the occurrence of major congenital anomalies (primary outcome) and selected pregnancy outcomes. The first interim analysis (performed using German pregnancy cohorts) was conducted when ⩾75 pregnant women (including 25 women from the maternal cohort exposed) were cumulatively reached across all participating countries. The end of the study period will be established once pregnancy counts reach 149 in the maternal cohort exposed and 298 in the maternal cohort unexposed in all countries combined, or 5 years after pregnancy counts are first assessed (whichever occurs first).</p><p><strong>Results: </strong>As of January 2024, data on pregnancies of women exposed to cladribine tablets (<i>n</i> = 28-36 (numbers are approximate due to masking of some counts)), and pregnancies of women unexposed to cladribine tablets (<i>n</i> = 2834) were available from Denmark, Finland, Germany, Scotland, and Sweden.</p><p><strong>Conclusion: </strong>The CLEAR study, using a staggered methodological approach, aims to provide further insight into the safety outcome data for cladribine tablets in pregnant women, as a regulatory commitment with the European Medicines Agency.</p><p><strong>Trial registration: </strong>EU PAS Register number, EUPAS25027.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241310996"},"PeriodicalIF":4.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vaccination coverage and its determinants in patients with multiple sclerosis-a multicenter cross-sectional study.","authors":"Paula Schade, Hai-Anh Nguyen, Julia Steinle, Kerstin Hellwig, Teodor Pelea, Philipp Franken, Birte Elias-Hamp, Veit Becker, Stefan Merkelbach, Stephan Richter, Bert Wagner, Christian Geis, Matthias Schwab, Florian Rakers","doi":"10.1177/17562864241309806","DOIUrl":"10.1177/17562864241309806","url":null,"abstract":"<p><strong>Background: </strong>Complete vaccination coverage is recommended by multiple sclerosis (MS) societies for patients with multiple sclerosis (pwMS) to mitigate infection risks associated with disease-modifying therapies (DMTs).</p><p><strong>Objectives: </strong>To analyze vaccination coverage and its determinants in pwMS compared to healthy controls, considering vaccination hesitancy, MS-specific vaccination beliefs, trust in information sources, and the role of general practitioners (GPs).</p><p><strong>Methods: </strong>This cross-sectional multicenter observational study was conducted in six German MS centers. The primary endpoint was a vaccination index (VI) comprising eight standard vaccinations (range 0-1, with higher VI indicating better vaccination coverage). Secondary endpoints included validated measures of general vaccination hesitancy, MS-specific vaccination beliefs, and trust in information sources. Data were collected through questionnaires, vaccination card analysis, and a survey of GPs who vaccinate pwMS.</p><p><strong>Results: </strong>VI tended to be lower in pwMS (<i>n</i> = 397) compared to healthy controls (<i>n</i> = 300; 0.58 ± 0.30 vs 0.62 ± 0.31, <i>p</i> = 0.057). In pwMS receiving highly effective DMTs, VI did not differ significantly from those on no/platform DMTs. Vaccination hesitancy was comparably low, with no differences between pwMS and controls. Vaccination hesitancy, beliefs, and trust in information sources explained only 10%-16% of the variance in VI. Among 109 GPs, 82% cited reluctance to vaccinate pwMS due to concerns about MS-related side effects or interactions with DMTs.</p><p><strong>Conclusion: </strong>Despite clear recommendations from MS societies for full vaccination of all pwMS, vaccination coverage remains worryingly low. Approximately half of the patients lack standard vaccination coverage, even those on highly effective DMTs. In fact, vaccination coverage in pwMS tended to be even lower than in healthy controls. Vaccination hesitancy and other intrinsic factors do not sufficiently explain the low vaccination rates. Inconsistent vaccination recommendations from GPs due to uncertainties about vaccine safety and DMT interactions likely contribute.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241309806"},"PeriodicalIF":4.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to \"Chronic active lesions in multiple sclerosis: classification, terminology, and clinical significance\".","authors":"","doi":"10.1177/17562864251316382","DOIUrl":"https://doi.org/10.1177/17562864251316382","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1177/17562864241306684.].</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251316382"},"PeriodicalIF":4.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral supplementation with propionate is reflected in the serum of healthy individuals.","authors":"Maximilian Schröder, Arijan Pasic, Frank Hirche, Svitlana Rozanova, Melissa Sgodzai, Barbara Gisevius, Lea Horstkemper, Ralf Gold, Katrin Marcus, Kalliopi Pitarokoili, Jeremias Motte, Katalin Barkovits, Gabriele Stangl, Anna Lena Fisse","doi":"10.1177/17562864241309755","DOIUrl":"10.1177/17562864241309755","url":null,"abstract":"<p><strong>Background: </strong>Short-chain fatty acids (SCFAs), including propionic acid (PA), are key in immunological research. Supplementing PA has shown benefits for autoimmune diseases. A comprehensive understanding of the PA pharmacokinetics is essential for the optimal design and execution of studies utilizing orally administered PA.</p><p><strong>Objective: </strong>We propose two methods of measuring PA in serum, carried out by different laboratories.</p><p><strong>Design: </strong>Blood samples from 20 volunteers were collected hourly following PA supplementation.</p><p><strong>Methods: </strong>Serum propionate quantification was performed with two independent mass spectrometry-based (MS) analyses, including liquid-chromatography (LC)-MS and direct-infusion (DI)-MS.</p><p><strong>Results: </strong>PA levels increased within 1 h of ingestion of 500 mg PA. Serum concentrations ranged from 1.3 to 4.5 µmol/L, rising significantly after 1 h (<i>p</i> < 0.05). Serum levels returned to baseline within 2 h. No significant differences were found regarding sex or diet.</p><p><strong>Conclusion: </strong>The shown pharmacokinetics can be used in future PA research.</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864241309755"},"PeriodicalIF":4.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tofersen and other antisense oligonucleotides in ALS.","authors":"Albert Ludolph, Maximilian Wiesenfarth","doi":"10.1177/17562864251313915","DOIUrl":"10.1177/17562864251313915","url":null,"abstract":"<p><p>The advent of antisense oligonucleotide (ASO) therapies in neurodegenerative disorders is associated with enormous hope. Nusinersen treatment was a breakthrough intervention in the recessive disease spinal muscular atrophy, and superoxide dismutase 1 (SOD1) amyotrophic lateral sclerosis (ALS) seems to be the paradigm disease in dominant degenerative diseases. The results of treatment with the ASO tofersen in SOD1-ALS show that the drug has a convincing beneficial effect on ALS caused by SOD1 mutations, that preclinical studies in rodents predicted the therapeutic effect in the human disease, and that clinical efficacy is associated with a specific sequence of effects of the drug on mechanistic and degenerative biomarkers and, subsequently, functional outcomes such as weight stabilization and ALSFRS-R. Therefore, the enthusiasm seems to be justified; but this should be followed by an attempt to obtain further insights with the goal to improve this therapy. In particular, the following issues are only partially resolved: Which mechanisms are responsible for the clinical effect following the downregulation of SOD1 protein by ASOs? Is long-term downregulation of SOD1 function associated with side effects? Is there an autoimmune response caused by this and other ASO? Is prevention of SOD1-associated ALS possible?</p>","PeriodicalId":22980,"journal":{"name":"Therapeutic Advances in Neurological Disorders","volume":"18 ","pages":"17562864251313915"},"PeriodicalIF":4.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}