Neurology and Therapy最新文献

{"title":"Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.","authors":"Michele Potashman, Katja Rudell, Naomi Suminski, Rinchen Doma, Maggie Heinrich, Linda Abetz-Webb, Melissa Wolfe Beiner, Vlad Coric, Liana S Rosenthal, Sheng-Han Kuo, Theresa Zesiewicz, Terry D Fife, Bart van de Warrenburg, Giovanni Ristori, Matthis Synofzik, Sub Subramony, Susan Perlman, Jeremy D Schmahmann, Gil L'Italien","doi":"10.1007/s40120-024-00704-8","DOIUrl":"10.1007/s40120-024-00704-8","url":null,"abstract":"<p><strong>Introduction: </strong>The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.</p><p><strong>Methods: </strong>Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA. Interviews were recorded, transcribed, coded, and analyzed by ATLAS.Ti v22 software.</p><p><strong>Results: </strong>FARS-ADL concepts most frequently reported by individuals with SCA were difficulty walking (n = 7/7), falls (n = 6/7), speech difficulties (n = 4/7), and swallowing (n = 3/7). Individuals with SCA reported that all FARS-ADL items were relevant; Gait and Walking (n = 7/7), Bladder Function (n = 6/7), and Falling (n = 6/7) were considered extremely relevant. All HCPs (n = 8/8) reported that most FARS-ADL items were relevant to individuals with SCA; Quality of Sitting Position was considered least relevant. HCPs reported meaningful change as 1-2 point score change in individual FARS-ADL items (n = 7/7), 1-3 point change in total score (n = 6/6), and stability on any item and/or total score over ≥ 1 year, depending on SCA subtype (n = 5/8). Cognitive debriefing supported clarity and comprehension of FARS-ADL. Suggested improvements included refining response options for Dressing, Falling, Walking, and Bladder Function items.</p><p><strong>Conclusion: </strong>The findings confirm the content validity of most FARS-ADL items for use in individuals with mild-to-moderate SCA1 and SCA3, and offer suggested improvements for response options.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"547-563"},"PeriodicalIF":3.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endovascular Treatment in Patients with Large Vessel Occlusion Stroke of Different Mechanisms.","authors":"Zhiyuan Feng, Ming Yang, Aoming Jin, Ning Ma, Feng Gao, Dapeng Mo, Xiaojuan Liu, Fangyuan Zhang, Xinchen Li, Yimeng Li, Qi Chu, Jing Xue, Aichun Cheng, Jinxi Lin, Hao Li, Xia Meng, Zhongrong Miao, Yongjun Wang, Jie Xu","doi":"10.1007/s40120-025-00727-9","DOIUrl":"10.1007/s40120-025-00727-9","url":null,"abstract":"<p><strong>Introduction: </strong>Acute ischemic stroke with large vessel occlusion (AIS-LVO) is mainly caused by in situ thrombosis (IST), artery-to-artery embolism (AAE), and cardioembolism (CE). The clinical characteristics and prognosis of each mechanism are unclear in a real-world scenario.</p><p><strong>Methods: </strong>We retrospectively analyzed patients with AIS-LVO who underwent endovascular treatment (EVT) between April 2023 and August 2024. Patients were classified according to three mechanisms. This study aimed to compare the clinical characteristics, lab results, EVT procedural factors, and prognosis of patients with AIS-LVO with three different mechanisms. The modified Rankin Scale (mRS) score at 3 months was the primary outcome, which was analyzed by ordinal logistic regression.</p><p><strong>Results: </strong>Among 162 patients included, IST (n = 81) was the most common mechanism, followed by CE (n = 41) and AAE (n = 40). Patients with CE showed more severe initial symptoms and the highest rate of intracranial hemorrhage. Patients with IST were associated with more rapid progression, more posterior circulation involvement, and higher inflammatory profile. Patients with AAE experienced a longer procedural time and had a higher rate of symptomatic intracranial hemorrhage (sICH). Although patients with IST and AAE more often required stenting, no significant difference in the rate of successful recanalization was found. The rates of mRS distribution (p = 0.24), and favorable outcomes at 3 months (p = 0.36) did not differ among the three groups. However, a trend towards better outcomes in the CE group was noted. On multivariable logistic regression, age (odds ratio, 0.97, 95% confidence interval, 0.95-1.00), pre-EVT National Institutes of Health Stroke Scale (NIHSS) (odds ratio, 0.94, 95% confidence interval, 0.89-0.98), and sICH (odds ratio, 0.33, 95% confidence interval, 0.12-0.95) could independently predict a favorable shift in mRS distribution. We failed to find that the mechanism was a predictor of the outcome.</p><p><strong>Conclusions: </strong>The functional outcomes of patients with AIS-LVO were similar among different mechanisms, despite the sICH being much higher in patients with AAE. The optimal management for AIS-LVO with different mechanisms requires further research.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lecanemab's Path Forward: Navigating the Future of Alzheimer's Treatment in Europe Amidst the EMA's Rejection.","authors":"Alessandro Martorana, Chiara Giuseppina Bonomi, Martina Gaia Di Donna, Caterina Motta","doi":"10.1007/s40120-024-00675-w","DOIUrl":"10.1007/s40120-024-00675-w","url":null,"abstract":"<p><p>Lecanemab (Leqembi^©, Biogen), a humanized anti-amyloid-beta monoclonal antibody, has been approved for early-stage Alzheimer's disease (AD) in several countries, including the US and Japan. However, the European Medicines Agency (EMA) recently issued a negative opinion on its marketing authorization, reflecting concerns over the clinical value and manageability of anti-amyloid treatments. This decision highlights the ongoing disconnect between research advancements and clinical practice, where the focus on biological markers over tangible clinical improvements remains contentious. Despite promising biological effects, lecanemab's clinical outcomes have been modest, raising questions about its therapeutic role. The EMA's refusal underscores the need to address doubts surrounding the real-world effectiveness and safety of such treatments, especially concerning amyloid-related imaging abnormalities (ARIAs), a common side effect observed in clinical trials. The recent approval of lecanemab by the UK's Medicines and Healthcare products Regulatory Agency, despite the National Institute for Health and Care Excellence's rejection on cost-effectiveness grounds, further fuels the debate on the feasibility of anti-amyloid therapies. This commentary emphasizes the importance of real-world data on lecanemab's impact on cognitive decline, daily functioning, and side-effect management. As the global clinical use of lecanemab increases, continuous and standardized reporting on its outcomes is crucial for guiding future regulatory decisions and for potentially bridging the gap between research and practice in AD treatment.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"1-5"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Novel Classification System and Prognostic Model for Open Traumatic Brain Injury: A Multicenter Retrospective Study.","authors":"Yuhui Chen, Li Chen, Liang Xian, Haibing Liu, Jiaxing Wang, Shaohuai Xia, Liangfeng Wei, Xuewei Xia, Shousen Wang","doi":"10.1007/s40120-024-00678-7","DOIUrl":"10.1007/s40120-024-00678-7","url":null,"abstract":"<p><strong>Introduction: </strong>Open traumatic brain injury (OTBI) is associated with high mortality and morbidity; however, the classification of these injuries and the determination of patient prognosis remain uncertain, hindering the selection of optimal treatment strategies. This study aimed to develop and validate a novel OTBI classification system and a prognostic model for poor prognosis.</p><p><strong>Methods: </strong>This retrospective study included patients with isolated OTBI who received treatment at three large medical centers in China between January 2020 and June 2022 as the training set. Data on patients with OTBI collected at the Fuzong Clinical Medical College of Fujian Medical University between July 2022 and June 2023 were used as the validation set. Clinical parameters, including clinical data at admission, radiological and laboratory findings, details of surgical methods, and prognosis were collected. Prognosis was assessed through a dichotomized Glasgow Outcome Scale (GOS). A novel OTBI classification was proposed, categorizing patients based on a combination of intracranial hematoma and midline shift observed on imaging, and logistic regression analyses were performed to identify risk factors associated with poor prognosis and to investigate the association between the novel OTBI classification and prognosis. Finally, a nomogram suitable for clinical application was established and validated.</p><p><strong>Results: </strong>Multivariable logistic regression analysis identified OTBI classification type C (p < 0.001), a Glasgow Coma Scale score (GCS) ≤ 8 (p < 0.001), subarachnoid hemorrhage (SAH) (p = 0.004), subdural hematoma (SDH) (p = 0.011), and coagulopathy (p = 0.020) as independent risk factors for poor prognosis. The addition of the OTBI classification to a model containing all the other identified prognostic factors improved the predictive ability of the model (Z = 1.983; p = 0.047). In the validation set, the model achieved an area under the curve (AUC) of 0.917 [95% confidence interval (CI) = 0.864-0.970]. The calibration curve closely approximated the ideal curve, indicating strong predictive performance of the model.</p><p><strong>Conclusions: </strong>The implementation of our proposed OTBI classification system and its use alongside the other prognostic factors identified here may improve the prediction of patient prognosis and aid in the selection of the most suitable treatment strategies.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"157-175"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Migraine on the Whole Life Course of Patients: Results from the OVERCOME (Japan) 2nd Study.","authors":"Daisuke Danno, Shiho Suzuki, Tsubasa Takizawa, Ryotaro Ishii, Masayuki Hamakawa, Yoshinori Tanizawa, Satoshi Osaga, Mika Komori","doi":"10.1007/s40120-024-00690-x","DOIUrl":"10.1007/s40120-024-00690-x","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of migraine on patients' lives, including challenges they face before getting access to appropriate medical management, is not well understood. The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE [OVERCOME (Japan)] 2nd study was conducted to provide information regarding burden and experience with migraine throughout the life course.</p><p><strong>Methods: </strong>This cross-sectional, population-based, nationwide online survey was conducted in adults with or without migraine. The migraine group reported their headache features and experiences in medical management since headache onset. Migraine's burden and impact were assessed with various PRO instruments. Migraine and non-migraine groups reported their experiences in life events and answered questions on self-esteem. Subgroup analyses by the number of monthly headache days (MHD) were performed.</p><p><strong>Results: </strong>The migraine group (n = 19,590) was numerically younger [mean (SD) age 40.5 (13.1) years vs. 53.1 (17.8) years] and included more females (68.8% vs. 52.1%) than the non-migraine group (n = 2219). The migraine group had mean (SD) 3.5 (5.2) MHDs; 24.2-56.7% had moderate-to-very severe disease burden per various PRO instruments. Headaches started when respondents with migraine were 17.8 years old; 86.7% started over-the-counter medications at 19.4 years of age. Only 46.4% self-reported migraine diagnosis by a physician and 25.1% received an oral preventive drug, almost a decade after headache onset. Up to 16.8% reported poor support/lack of understanding from either teachers or parents during school life. The migraine group had numerically more frequent job changes and divorce, and lower self-esteem, than the non-migraine group. Across assessments, increased MHDs tended to worsen outcomes.</p><p><strong>Conclusion: </strong>Migraine affected many individuals from an early stage, but timely support and medical intervention were insufficient. This may negatively impact important life events, cause long-term impairment, and decrease self-esteem. Hence, improving the social understanding and medical environment for migraine to provide timely support is essential.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"335-356"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Pharmacokinetics of Atogepant in Healthy Japanese and White Adults.","authors":"Ramesh R Boinpally, Brian McNamee","doi":"10.1007/s40120-024-00699-2","DOIUrl":"10.1007/s40120-024-00699-2","url":null,"abstract":"<p><strong>Introduction: </strong>Atogepant is a calcitonin gene-related peptide receptor antagonist approved for the preventive treatment of migraine in adults in the USA, EU, and several other countries. The objectives of this study were to evaluate the pharmacokinetics (PK) and dose proportionality of atogepant in healthy Japanese participants, evaluate the safety and tolerability of atogepant in Japanese participants, and explore the differences in the PK and safety of atogepant in Japanese vs white participants.</p><p><strong>Methods: </strong>A total of 50 participants (40 Japanese and 10 white) were enrolled into five cohorts; Japanese cohorts were randomized in a 4:1 ratio to atogepant (10 mg, 30 mg, or 60 mg daily dosing and 60 mg twice daily) or placebo. The white participants were randomized to atogepant (60 mg twice daily) or placebo. Doses were administered on day 1 and days 3-8, with those on days 1 and 8 administered after an overnight fast.</p><p><strong>Results: </strong>In Japanese participants, atogepant exposure increased with dose, and there was no accumulation with once-daily dosing and minimal (~ 20%) accumulation with twice-daily dosing. Atogepant steady-state exposure appeared to be marginally lower in Japanese participants compared with white participants and was well tolerated. There were no treatment-related adverse events, serious adverse events, clinically significant changes in vital signs, or signs of suicidal ideation or behaviors.</p><p><strong>Conclusion: </strong>Atogepant exposure increased with dose in healthy Japanese participants and was well tolerated within the dose range tested.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"399-412"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TEC-ADHERE: Real-World Persistence and Adherence on Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis in the French OroSEP Patient-Support Program.","authors":"Pierre Labauge, Alain Créange, Thibault Moreau, Jocelyne Nouvet-Gire, Bernard Pedespan, Olivier Heinzlef, Nathalie Texier, Marilyn Gros, Catherine Marti, Marta Ruiz, Mikel Martinez, Giovanni Castelnovo","doi":"10.1007/s40120-024-00674-x","DOIUrl":"10.1007/s40120-024-00674-x","url":null,"abstract":"<p><strong>Introduction: </strong>Treatment persistence and adherence are essential for achieving therapeutic goals in patients with multiple sclerosis (MS). OroSEP is an independent patient-support program (PSP) in France for patients with relapsing-remitting MS (RRMS) receiving oral disease-modifying therapies.</p><p><strong>Methods: </strong>TEC-ADHERE (NCT04221191; 08/19/2019-09/15/2022) was a prospective, non-interventional, phase 4 study to assess the effect of OroSEP on persistence and adherence to dimethyl fumarate (DMF; Tecfidera™) in patients with RRMS. Outcomes were compared for patients in OroSEP versus non-OroSEP patients who received their neurologists' standard of care (SoC). Patients initiated DMF at month 0 (M0); follow-up visits occurred at M3 and M6. Primary outcome was persistence at M6. Secondary outcomes included persistence at M1 and M3, adherence at M6 (Girerd questionnaire), anxiety (Generalized Anxiety Disorder Assessment), patient satisfaction at M6 (Treatment Satisfaction Questionnaire for Medication), patient and neurologist satisfaction with OroSEP participation, and adverse events (AEs).</p><p><strong>Results: </strong>Per-protocol population included 341 patients (OroSEP, n = 135; SoC, n = 206). Persistence was similar for OroSEP vs SoC (M6, 75.9% vs 76.6%; M1, 96.0% vs 92.4%; M3, 85.5% vs 89.0%). At M6, mean adherence was higher for OroSEP (5.4) vs SoC (4.7; p < 0.0001), and good adherence (Girerd score = 6) was achieved by more OroSEP patients (55.7%) than SoC patients (29.6%; p < 0.01). Mean anxiety scores were lower in the OroSEP group than in the SoC group at baseline (7.1 vs 8.8; p = 0.02) and M6 (3.4 vs 6.1; p < 0.001). Mean satisfaction scores at M6 were higher for OroSEP (77.4) vs SoC (64.2; p < 0.01). Most neurologists (n = 11/14) agreed that OroSEP helped improve adherence. Treatment-related AEs occurred in 62 (36.3%) OroSEP patients and 76 (42.9%) SoC patients; most common were flushing, diarrhea, hot flush, and abdominal pain.</p><p><strong>Conclusion: </strong>These outcomes support the value of PSPs in encouraging adherence, alleviating anxiety, improving patient satisfaction, and supporting patients to be more independent in managing MS.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT04221191.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"177-192"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Caregiver Global Impression Observations from EMBARK: A Phase 3 Study Evaluating Delandistrogene Moxeparvovec in Ambulatory Patients with Duchenne Muscular Dystrophy.","authors":"Craig M McDonald, Jacob S Elkins, Sai Dharmarajan, Katherine Gooch, Teofil Ciobanu, Claire J Lansdall, Alexander P Murphy, Fiona McDougall, Eugenio M Mercuri, Ivana Audhya","doi":"10.1007/s40120-024-00685-8","DOIUrl":"10.1007/s40120-024-00685-8","url":null,"abstract":"<p><strong>Introduction: </strong>Duchenne muscular dystrophy (DMD) is a rare, progressive, debilitating neuromuscular disease. The early childhood onset and debilitating nature of the disease necessitate decades of caretaking for most patients. Caregivers have a critical role in evaluating patients' physical functioning and/or response to treatment. Using DMD-specific caregiver-reported scales, the impact of delandistrogene moxeparvovec gene therapy on caregivers' perceived change in patient disease status or severity was evaluated using the Caregiver Global Impression of Change and Severity (CaGI-C and CaGI-S, respectively).</p><p><strong>Methods: </strong>In the Phase 3 randomized, double-blind, placebo-controlled trial (EMBARK; NCT05096221), the CaGI-C at week 52 and change from baseline to week 52 in CaGI-S were evaluated in a post hoc analysis. The CaGI-C assesses caregivers' impressions of change in DMD symptoms, physical ability, ability to perform daily activities, and overall health. The CaGI-S evaluates current severity of DMD symptoms, physical ability, ability to perform activities of daily living, and overall health. Data were evaluated using multi-domain responder index (MDRI) and ordinal regression analyses.</p><p><strong>Results: </strong>MDRI analyses across all four CaGI-C items yielded a treatment difference of 1.7 (95% confidence interval [CI]: 0.90-2.5) favoring delandistrogene moxeparvovec; a treatment difference of 1.1 (95% CI 0.30-1.9) was observed for the CaGI-S favoring delandistrogene moxeparvovec. After adjusting for age, ordinal regression analysis showed a nominally significant increase in the odds of achieving a better rating for delandistrogene moxeparvovec-treated patients on all four CaGI-C items (≥ 3.8-fold increase). After adjusting for baseline severity and age, ordinal regression analysis showed a nominally significant increase in the odds of improvement on all four CaGI-S items (≥ 2.2-fold increase).</p><p><strong>Conclusion: </strong>These exploratory findings captured by caregiver-reported outcomes add to the totality of evidence that supports the clinical benefits of delandistrogene moxeparvovec for patients with DMD.</p><p><strong>Trial registration number: </strong>ClinicalTrials.gov identifier, NCT05096221.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"211-225"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Tolerability and Pharmacokinetic-Pharmacodynamic Relationship of NX210c Peptide in Healthy Elderly Volunteers: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study.","authors":"Annette Janus, Daniël Dumas, Juliette Le Douce, Sébastien Marie, Giuseppe Pasculli, Pauline Bambury, Sighild Lemarchant, Philip Kremer, Yann Godfrin","doi":"10.1007/s40120-024-00691-w","DOIUrl":"10.1007/s40120-024-00691-w","url":null,"abstract":"<p><strong>Introduction: </strong>Blood-brain barrier (BBB) integrity is fundamental to brain homeostasis, enabling control of substance exchange and safeguarding neurons against harmful toxins, pathogens, and immune cells that lead to dysregulation and inflammation involved in ageing and neurodegenerative diseases (NDD). The cyclized peptide NX210c is a thrombospondin type 1 repeat analogue derived from subcommissural organ-spondin. It exerts beneficial effects in animal models of NDD owing to its effects on neurons and endothelial cells. NX210c demonstrated a good safety profile in a single ascending dose phase 1a clinical study. The present multiple ascending dose phase 1b study was performed to evaluate the tolerability and pharmacological effects of repeated doses of NX210c in healthy elderly (age: > 55 years) volunteers.</p><p><strong>Methods: </strong>This was a randomized, placebo-controlled, double-blind study (EudraCT No. 2022-002868-76), investigating safety/tolerability, pharmacokinetics, and pharmacodynamics (including blood and cerebrospinal fluid biomarkers). Participants received 5 or 10 mg/kg NX210c or placebo (10-min infusion) thrice weekly for 4 weeks in an ascending dose fashion. Follow-up was conducted 2 weeks after last dosing.</p><p><strong>Results: </strong>The investigation included 29 participants. No serious adverse events were recorded and all adverse events were mild. Dedicated central nervous system testing did not reveal neurotoxicity. Biomarker evaluation showed a statistically significant reduction in blood claudin-5 and a trend toward reduction of blood homocysteine. In silico data modelling revealed salient pharmacokinetic-pharmacodynamic relationships, including reduction of claudin-5, neurofilament light chain, and SPARC-like protein 1 release, and degradation of homocysteine.</p><p><strong>Conclusion: </strong>Multiple doses of NX210c exhibited a good safety profile, showed non-cumulative pharmacokinetics, and exerted pharmacodynamic effects on biomarkers linked to BBB integrity. The effects of NX210c on claudin-5 and biomarkers influencing BBB integrity-and the overarching brain protection it offers-provide a novel therapeutic strategy targeting an underlying driver of neurodegenerative conditions for which disease-modifying treatments are limited or not available.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"357-377"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in Parkinson's Disease: A Narrative Review.","authors":"Carlo Cattaneo, Javier Pagonabarraga","doi":"10.1007/s40120-024-00687-6","DOIUrl":"10.1007/s40120-024-00687-6","url":null,"abstract":"<p><p>Sex differences in epidemiology, clinical features, and therapeutical responses are emerging in several movement disorders, even though they are still not widely recognized. Parkinson's disease (PD) is not an exception: men and women suffering from PD have different levels of disability. Research has been performed using multiple databases and scientific journals; this review summarizes the available evidence on sex differences in PD regarding epidemiology, risk factors, genetics, clinical phenotype, social impact, and therapeutic management. The role of hormones in determining such differences is also briefly discussed. The results confirm the existence of differences between men and women in PD; women have a higher risk of developing disabling motor complications and non-motor fluctuations compared to men, while men have a higher risk of developing cognitive impairment, postural instability, and gait disorders. Improving our knowledge in these differences may result in the implementation of strategies for disease-tailored treatment and management.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"57-70"},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}