Annals of Clinical and Translational Neurology最新文献_第4页

Analysis of Soluble Interleukin-2 Receptor as a Prognostic Biomarker in NMOSD and MOGAD. 可溶性白介素-2受体作为NMOSD和MOGAD预后生物标志物的分析。

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-09-05 DOI: 10.1002/acn3.70186

Philipp Klyscz, Carolin Otto, Klemens Ruprecht, Susanna Asseyer, Hannes Ole Tiedt, Christian Meisel, Judith Bellmann-Strobl, Friedemann Paul, Patrick Schindler

{"title":"Analysis of Soluble Interleukin-2 Receptor as a Prognostic Biomarker in NMOSD and MOGAD.","authors":"Philipp Klyscz, Carolin Otto, Klemens Ruprecht, Susanna Asseyer, Hannes Ole Tiedt, Christian Meisel, Judith Bellmann-Strobl, Friedemann Paul, Patrick Schindler","doi":"10.1002/acn3.70186","DOIUrl":"https://doi.org/10.1002/acn3.70186","url":null,"abstract":"Objective: Soluble interleukin-2 receptor (sIL-2R) is a biomarker for T cell activity. T cells are involved in neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) pathogenesis. However, sIL-2R has so far not been evaluated in these conditions. Here, we compared sIL-2R levels in serum and cerebrospinal fluid (CSF) of patients with aquaporin-4-IgG-seropositive and seronegative (AQP4-IgG+/-) NMOSD, MOGAD, and noninflammatory neurologic disorders (NINDs), and assessed the prognostic value of sIL-2R for future attacks.Methods: Retrospective analysis of real-world data of patients treated at Charité-Universitätsmedizin Berlin was conducted (45 MOGAD, 14 AQP4-IgG+NMOSD, 10 AQP4-IgG-NMOSD, 69 NINDs) between 2010 and 2024. Mean (SD) follow-up time was 40 (35) months. sIL-2R differences were assessed by linear mixed models. Cox regression analysis was performed to investigate the predictive value for subsequent attacks.Results: Serum sIL-2R was higher in AQP4-IgG+NMOSD (estimated marginal mean [EMM] 802 IU/mL) and MOGAD (569 IU/mL) compared to NINDs (404 IU/mL). In patients with a first manifestation of MOGAD, but not NMOSD, serum sIL-2R (HR = 9.07 [95% CI 1.37-60.01]) and CSF sIL-2R (HR = 3.27 [95% CI 0.61-17.45]) levels were predictive for subsequent attacks.Interpretation: Serum sIL-2R is elevated in AQP4-IgG+NMOSD and MOGAD and may be a prognostic biomarker for a relapsing disease course in MOGAD.","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Plasma Glial Fibrillary Acidic Protein Correlates With Brain Metal Burden in Wilson's Disease. 肝豆状核变性患者血浆胶质纤维酸性蛋白与脑金属负荷相关

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-09-05 DOI: 10.1002/acn3.70177

Sung-Pin Fan, Ya-Fang Chen, Cheng-Hsuan Li, Yih-Chih Kuo, Ni-Chung Lee, Yin-Hsiu Chien, Wuh-Liang Hwu, Tai-Chung Tseng, Tung-Hung Su, Chien-Ting Hsu, Huey-Ling Chen, Chin-Hsien Lin, Yen-Hsuan Ni

{"title":"Plasma Glial Fibrillary Acidic Protein Correlates With Brain Metal Burden in Wilson's Disease.","authors":"Sung-Pin Fan, Ya-Fang Chen, Cheng-Hsuan Li, Yih-Chih Kuo, Ni-Chung Lee, Yin-Hsiu Chien, Wuh-Liang Hwu, Tai-Chung Tseng, Tung-Hung Su, Chien-Ting Hsu, Huey-Ling Chen, Chin-Hsien Lin, Yen-Hsuan Ni","doi":"10.1002/acn3.70177","DOIUrl":"https://doi.org/10.1002/acn3.70177","url":null,"abstract":"Objective: Neuroinflammation driven by extracellular copper contributes to neuronal damage in Wilson's disease (WD). This study investigated the relationship between brain metal burden and peripheral neuroinflammation markers in WD.Methods: We conducted a cross-sectional study involving 89 participants, including patients with WD (n = 63), asymptomatic ATP7B heterozygous carriers (n = 12), and age/sex-matched controls (n = 14). Brain metal burden was assessed using quantitative susceptibility mapping (QSM) MRI. Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels were measured. Clinical severity was evaluated using the mini-Unified Wilson's Disease Rating Scale (UWDRS) and Montreal Cognitive Assessment (MoCA). The influence of copper chelation treatment on biomarker correlations was also examined.Results: Patients with WD had a significantly higher level of GFAP (p = 0.02) and brain metal burden (p < 0.01) than the control group. Plasma NfL levels were marginally elevated in the WD group (p = 0.07). Notably, elevated plasma GFAP levels were significantly associated with higher UWDRS scores (r = 0.35, p < 0.01) and lower MoCA scores (r = -0.36, p < 0.01). The NfL levels were also correlated with UWDRS (r = 0.58, p < 0.01) and marginally correlated with MoCA (r = -0.32, p = 0.02). The brain magnetic susceptibility value was positively correlated with increased plasma GFAP level, particularly in the putamen (p < 0.001), which was more prominent in WD patients without chelating agent treatment (r = 0.58, p < 0.001).Interpretations: Plasma GFAP levels reflect both clinical severity and brain metal accumulation in WD, with this association influenced by copper chelation therapy.","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long COVID in People With Multiple Sclerosis and Related Disorders: A Multicenter Cross-Sectional Study. 多发性硬化症和相关疾病患者的长COVID：一项多中心横断面研究

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-09-05 DOI: 10.1002/acn3.70184

Chen Hu, Jiyeon Son, Lindsay McAlpine, Elizabeth L S Walker, Megan Dahl, Emily Song, Sugeidy Ferreira Brito, Katelyn Kavak, Kaho Onomichi, Amit Bar-Or, Christopher Perrone, Claire S Riley, Bianca Weinstock-Guttman, Philip L De Jager, Erin E Longbrake, Zongqi Xia

{"title":"Long COVID in People With Multiple Sclerosis and Related Disorders: A Multicenter Cross-Sectional Study.","authors":"Chen Hu, Jiyeon Son, Lindsay McAlpine, Elizabeth L S Walker, Megan Dahl, Emily Song, Sugeidy Ferreira Brito, Katelyn Kavak, Kaho Onomichi, Amit Bar-Or, Christopher Perrone, Claire S Riley, Bianca Weinstock-Guttman, Philip L De Jager, Erin E Longbrake, Zongqi Xia","doi":"10.1002/acn3.70184","DOIUrl":"10.1002/acn3.70184","url":null,"abstract":"Background: Managing long COVID in people with multiple sclerosis and related disorders (pwMSRD) is complex due to overlapping symptoms. To address evidence gaps, we evaluated long COVID susceptibility in pwMSRD versus controls and its associations with multi-domain function and disability.Methods: In this multicenter cross-sectional study, participants completed a survey covering 71 post-infection symptoms, distinguishing new-onset from worsening symptoms. We defined long COVID using the 2024 NASEM criteria. Logistic regression assessed long COVID odds. Linear and Poisson regression evaluated associations with function and disability.Results: 969 pwMSRD (82.5% female, mean age 51.8 years, 63.5% infected) and 1003 controls (79.4% female, mean age 45.2 years, 61.2% infected) were included. PwMSRD had higher odds of long COVID (aOR = 1.6 [1.2-2.1]), with a stronger association when restricting to worsening symptoms (aOR = 2.3 [1.7-3.1]). Having long COVID was associated with worse physical function, cognition, and depression in both groups. PwMSRD with long COVID experienced greater physical function declines and more depression severity exacerbation than controls, and had faster disability progression compared to those without long COVID.Conclusion: PwMSRD show increased susceptibility to long COVID, primarily driven by worsening symptoms. Long COVID contributes to more functional decline and disability worsening. Recognizing and managing long COVID is essential for pwMSRD.","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chronic Pain in Parkinson's Disease: Prevalence, Sex Differences, Regional Anatomy and Comorbidities. 帕金森病的慢性疼痛：患病率、性别差异、区域解剖和合并症。

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-09-03 DOI: 10.1002/acn3.70174

Natalia S Ogonowski, Freddy Chafota, Fangyuan Cao, Amanda Wei Yin Lim, Victor Flores-Ocampo, Santiago Díaz-Torres, Zuriel Ceja, Luis M García-Marín, Scott F Farrell, Kishore R Kumar, Jane Alty, George D Mellick, Trung Thành Ngô, Miguel E Rentería

{"title":"Chronic Pain in Parkinson's Disease: Prevalence, Sex Differences, Regional Anatomy and Comorbidities.","authors":"Natalia S Ogonowski, Freddy Chafota, Fangyuan Cao, Amanda Wei Yin Lim, Victor Flores-Ocampo, Santiago Díaz-Torres, Zuriel Ceja, Luis M García-Marín, Scott F Farrell, Kishore R Kumar, Jane Alty, George D Mellick, Trung Thành Ngô, Miguel E Rentería","doi":"10.1002/acn3.70174","DOIUrl":"10.1002/acn3.70174","url":null,"abstract":"Objective: Chronic pain is prevalent among people living with Parkinson's disease (PD). We analyzed data from 10,631 Australian individuals with PD to assess the prevalence, age and sex differences, severity, anatomical distribution, clinical history, and associated factors.Methods: We analysed data from 10,631 participants with PD enrolled in the Australian Parkinson's Genetics Study (APGS), an ongoing nationwide cohort. Participants completed an online or paper-based questionnaire assessing sociodemographic factors, PD-related variables, and chronic pain characteristics. Chronic pain was defined as pain persisting for more than 3 months and occurring most days or daily. Statistical analyses included descriptive statistics, correlation analyses, and group comparisons using chi-squared tests, Fisher's exact tests, and independent samples t-tests.Results: Two-thirds (66.2%) reported chronic pain, with females experiencing higher prevalence (70.8%) and severity (4.7 vs. 4.3 on a 10-point scale). Common pain sites included the buttocks (35.6%), lower back (25.4%), neck (19.4%), and knees (17.2%). Chronic pain was strongly linked to comorbid depression, sleep disorders, and osteoarthritis (p < 0.05). Environmental exposures such as pesticides, heavy metals, and alcohol were associated with higher pain prevalence, especially in males (p < 0.05).Interpretation: These findings emphasise the substantial burden of chronic pain in PD, highlighting sex differences and strong links to multimorbidity. Further research is warranted to clarify sex-specific treatments and identify novel therapeutic targets.","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CSF Mitochondrial DNA: Biomarker of Body Composition and Energy Metabolism in Parkinson's Disease. 脑脊液线粒体DNA：帕金森病患者身体组成和能量代谢的生物标志物。

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-09-01 DOI: 10.1002/acn3.70183

Yasuaki Mizutani, Tsuyoshi Nakai, Yasuhiro Maeda, Reiko Ohdake, Atsuhiro Higashi, Toshiki Maeda, Ryunosuke Nagao, Sayuri Shima, Kazuya Kawabata, Akihiro Ueda, Mizuki Ito, Hirohisa Watanabe

{"title":"CSF Mitochondrial DNA: Biomarker of Body Composition and Energy Metabolism in Parkinson's Disease.","authors":"Yasuaki Mizutani, Tsuyoshi Nakai, Yasuhiro Maeda, Reiko Ohdake, Atsuhiro Higashi, Toshiki Maeda, Ryunosuke Nagao, Sayuri Shima, Kazuya Kawabata, Akihiro Ueda, Mizuki Ito, Hirohisa Watanabe","doi":"10.1002/acn3.70183","DOIUrl":"https://doi.org/10.1002/acn3.70183","url":null,"abstract":"Objective: Cerebrospinal fluid (CSF) cell-free mitochondrial DNA (cf-mtDNA) is a potential biomarker for Parkinson's disease (PD), but its clinical relevance remains unclear. We investigated associations between CSF cf-mtDNA levels, body composition, nutritional status, and metabolic biomarkers in PD.Methods: CSF cf-mtDNA levels, defined as the copy numbers of two regions of the mtDNA circular molecule (mt64-ND1 and mt96-ND5), were quantified in 44 PD patients and 43 controls using multiplex digital PCR. The mt96-ND5/mt64-ND1 ratio was calculated to estimate mtDNA deletion burden. Associations with clinical features, body composition, serum nutritional markers, and plasma energy metabolism-related organic acids were examined. Generalized linear models (GLMs) were performed to adjust for confounders.Results: CSF mt64-ND1 and mt96-ND5 levels were lower in PD patients than controls (p = 0.002, p = 0.001), while the mt96-ND5/mt64-ND1 ratio showed no group difference. GLM analysis identified body composition indices and serum albumin as key determinants of cf-mtDNA levels. Subgroup analysis showed lower cf-mtDNA levels in PD patients with preserved body composition and nutritional status. The mt96-ND5/mt64-ND1 ratio displayed a biphasic association with body composition and an inverse correlation with plasma 2-ketoglutaric acid, suggesting a link to energy metabolism.Interpretation: CSF cf-mtDNA levels are reduced in PD and influenced by body composition and nutritional status, supporting their role as a metabolic biomarker. While the cf-mtDNA deletion ratio remained unchanged, its association with body composition suggests a complex interplay between mitochondrial integrity and metabolism. These findings highlight the relevance of cf-mtDNA in PD pathophysiology and the need for further study.","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Practice Recommendations for Genetic Testing of Ataxias. 共济失调基因检测的实践建议。

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-08-29 DOI: 10.1002/acn3.70171

Sharan R Srinivasan, Amy D Mook, Michelle Rochman, Jin Yun Helen Chen, Weiyi Mu, George R Wilmot, Liana S Rosenthal, Wendy R Uhlmann

{"title":"Practice Recommendations for Genetic Testing of Ataxias.","authors":"Sharan R Srinivasan, Amy D Mook, Michelle Rochman, Jin Yun Helen Chen, Weiyi Mu, George R Wilmot, Liana S Rosenthal, Wendy R Uhlmann","doi":"10.1002/acn3.70171","DOIUrl":"https://doi.org/10.1002/acn3.70171","url":null,"abstract":"Objective: Over the past decade, significant advances in genetic testing for ataxia have improved diagnostic accuracy, informed clinical trial eligibility, guided treatment decisions, and enabled cascade testing of at-risk relatives. While guidance exists for other neurogenetic conditions, there are no standardized guidelines on genetic counseling and testing for individuals with unexplained ataxia.Methods: We conducted a comprehensive literature review on genetic counseling and testing in ataxia, identifying 7362 articles. After removing 2971 duplicates, 4391 articles were screened by two authors using the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) framework. In areas lacking clear published evidence, we convened a multidisciplinary expert panel with clinical and genetic expertise in ataxia. Following conflict resolution and additional filtering, 68 articles were included in our guidance development.Results: Based on this evidence and expert consensus, we developed 20 recommendations addressing indications for genetic testing in hereditary ataxia, components of pre- and post-test counseling, testing options, insurance considerations, interpretation of test results, and appropriate referral to genetic counseling services. Major themes include the importance of formal genetic counseling and suggesting whole genome sequencing as first-line testing, with an emphasis on detecting repeat expansions.Conclusion: These evidence-based, consensus-driven recommendations aim to support clinicians in evaluating patients with unexplained ataxia in order to provide timely evaluation and care, both for patients and their at-risk relatives.","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-Cell RNA Seq in Sydenham Chorea Shows B Cell HLA-DR/DQ Upregulation and Plasma Cell Proteasomal Activation. Sydenham舞蹈病的单细胞RNA序列显示B细胞HLA-DR/DQ上调和浆细胞蛋白酶体激活。

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-08-26 DOI: 10.1002/acn3.70179

Velda X Han, Brooke A Keating, Brian S Gloss, Xianzhong Lau, Ruwani Dissanayake, Hiroya Nishida, Jessica Hayes, Shrujna Patel, Shekeeb S Mohammad, Russell C Dale

引用次数: 0

Durability of Response to B-Cell Maturation Antigen-Directed mRNA Cell Therapy in Myasthenia Gravis. 重症肌无力患者对b细胞成熟抗原引导的mRNA细胞治疗反应的持久性。

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-08-26 DOI: 10.1002/acn3.70167

Nizar Chahin, Gregory Sahagian, Marc H Feinberg, C Andrew Stewart, Christopher M Jewell, Metin Kurtoglu, Miloš D Miljković, Tuan Vu, Tahseen Mozaffar, James F Howard

{"title":"Durability of Response to B-Cell Maturation Antigen-Directed mRNA Cell Therapy in Myasthenia Gravis.","authors":"Nizar Chahin, Gregory Sahagian, Marc H Feinberg, C Andrew Stewart, Christopher M Jewell, Metin Kurtoglu, Miloš D Miljković, Tuan Vu, Tahseen Mozaffar, James F Howard","doi":"10.1002/acn3.70167","DOIUrl":"https://doi.org/10.1002/acn3.70167","url":null,"abstract":"Objective: We report the 12-month follow-up outcomes from a Phase 2 clinical trial (NCT04146051) evaluating Descartes-08, a BCMA-directed RNA chimeric antigen receptor T-cell (rCAR-T) therapy for refractory generalized myasthenia gravis (MG). These findings provide insight into the potential applicability of BCMA-targeted rCAR-T therapy for antibody-mediated autoimmune diseases.Methods: In the Phase 2a part of the study, Descartes-08 was administered at 52.5 × 106 CAR+ cells/kg per infusion with varying dosing frequencies as an outpatient treatment and without lymphodepletion chemotherapy. A subset of participants received Descartes-08 as six weekly infusions and were followed long term with assessments conducted at 2, 3, 6, 9, and 12 months.Results: All seven participants who received six weekly infusions of Descartes-08 exhibited clinically meaningful improvement in common MG severity scales (MG Composite, MG Activities of Daily Living, Quantitative MG scores, and Quality of Life 15-revised) at Month 3 without significant toxicity. At Month 9 follow-up, all participants continued to experience marked clinically meaningful improvements. Five out of seven participants maintained the response at Month 12. A third participant experienced a relapse approximately 6 months after completing on-study follow-up. All three participants who experienced loss of clinical effects were retreated. Two had rapid improvement in clinical scores with minimal symptom expression at Week 8, which was maintained through 12 months of retreatment follow-up. The third participant experienced similar improvement in MG severity scores to their initial treatment.Interpretation: These data support continued development of Descartes-08 in myasthenia gravis and other autoantibody-associated autoimmune disorders.","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Real World Effectiveness and Tolerability of Novel Monoclonal Antibodies and Rituximab for NMOSD. 新型单克隆抗体和利妥昔单抗治疗NMOSD的实际有效性和耐受性。

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-08-22 DOI: 10.1002/acn3.70160

Zarmina Javed, Mengke Du, Mary Rensel, Le H Hua, Carrie M Hersh, Justin R Abbatemarco, Devon S Conway, Daniel Ontaneda, Jeffrey A Cohen, Amy Kunchok

引用次数: 0

SYHA1813, A VEGFR and CSF1R Inhibitor, in Patients With Recurrent High-Grade Gliomas: A Multicenter, Open-Label Phase I Study. SYHA1813，一种VEGFR和CSF1R抑制剂，用于复发性高级别胶质瘤患者：一项多中心、开放标签的I期研究

IF 3.9 2区医学

Annals of Clinical and Translational Neurology Pub Date : 2025-08-22 DOI: 10.1002/acn3.70166

Zhuang Kang, Shenglan Li, Liang Wang, Qianxue Chen, Weiguo Hu, Ting Lei, Ying Mao, Jing Zhang, Xiaojun Xiang, Qiming Wang, Zhengwen He, Tao Sun, Yulei Wang, Mengqian Huang, Rong Zhang, Feng Chen, Wenbin Li

{"title":"SYHA1813, A VEGFR and CSF1R Inhibitor, in Patients With Recurrent High-Grade Gliomas: A Multicenter, Open-Label Phase I Study.","authors":"Zhuang Kang, Shenglan Li, Liang Wang, Qianxue Chen, Weiguo Hu, Ting Lei, Ying Mao, Jing Zhang, Xiaojun Xiang, Qiming Wang, Zhengwen He, Tao Sun, Yulei Wang, Mengqian Huang, Rong Zhang, Feng Chen, Wenbin Li","doi":"10.1002/acn3.70166","DOIUrl":"https://doi.org/10.1002/acn3.70166","url":null,"abstract":"Objective: Recurrent high-grade gliomas have a poor prognosis and limited therapeutic options. This study aimed to evaluate the safety and efficacy of SYHA1813, a dual inhibitor of VEGFR and CSF1R, in patients with recurrent high-grade gliomas.Methods: Eligible patients (aged ≥ 18) with histologically or cytologically confirmed recurrent high-grade gliomas were included. Patients were administered different doses of SYHA1813 daily to assess its safety and initial efficacy.Results: Sixty-four individuals with high-grade gliomas were enrolled. Treatment-related adverse events (TRAEs) were reported in 92.2% of the patients, with 40.6% experiencing grade 3 or higher TRAEs. No grade 5 TRAE was reported. The overall objective response rate (ORR) and disease control rate (DCR) were 18.8% (95% confidence interval [CI], 10.1-30.5) and 51.6% (95% CI, 38.7-64.3), respectively. With a median follow-up duration of 9.5 months, the median progression-free survival (PFS) was 2.8 months (95% CI, 2.3-4.2) with PFS-6 of 22.5% (95% CI, 11.8-35.4) and the median OS was 15.1 months (95% CI, 10.2-NE) with OS-12 of 63.3% (95% CI, 49.3-74.4). Among the 38 patients with glioblastoma, the ORR was 18.4% (95% CI, 7.7-34.3), with a DCR of 52.6% (95% CI, 35.8-69.0). The median PFS and OS were 4.1 months (95% CI, 2.3-5.3) and 13.0 months (95% CI, 9.1-NE), respectively. SYHA1813 was detected in cerebrospinal fluid samples and the drug concentration to plasma free drug concentration ratio was 0.30-1.27.Interpretation: SYHA1813 exhibits encouraging anti-tumor activity with a manageable safety profile for the treatment of recurrent high-grade gliomas, especially glioblastoma.Trial registration: chictr.org.cn (ChiCTR2100045380).","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0