Current Opinion in Neurology最新文献_第9页

Amyotrophic lateral sclerosis in Mainland China: clinical translational challenges and opportunities. 肌萎缩性侧索硬化症在中国大陆：临床转化的挑战和机遇。

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1097/WCO.0000000000001421

Ji He, Dongsheng Fan

{"title":"Amyotrophic lateral sclerosis in Mainland China: clinical translational challenges and opportunities.","authors":"Ji He, Dongsheng Fan","doi":"10.1097/WCO.0000000000001421","DOIUrl":"10.1097/WCO.0000000000001421","url":null,"abstract":"Purpose of review: Amyotrophic lateral sclerosis (ALS) imposes a growing medical and socioeconomic burden in China. This review synthesizes recent advances in understanding ALS epidemiology, biomarker discovery, therapeutic innovations, and policy frameworks in China. It highlights the urgency of addressing challenges, including fragmented healthcare resources, translational medicine gaps, and regional inequities, while emphasizing China's unique contributions to global ALS research.Recent findings: Chinese ALS cohorts exhibit distinct epidemiological profiles, including a younger mean age of onset and prolonged median survival. Policy initiatives, such as ALS inclusion in rare disease registries and insurance reforms, aim to reduce financial burdens of patients. Multimodal biomarker exploration has advanced integrated diagnostic models combining neurofilament light chain (NfL) and clinical data platforms. Neuroimaging and electrophysiological studies reveal glymphatic dysfunction, white matter degeneration, and neuromuscular junction abnormalities, with novel links to hepatic metabolism. Genomic analyses identify population-specific variants. Therapeutic innovations in China include not only biopharmaceuticals, but also integrative traditional Chinese medicine (TCM) approaches.Summary: China's ALS landscape is transitioning towards precision medicine through biomarker-guided diagnostics and multidisciplinary care models. Key priorities include establishing a national ALS registry, standardizing biomarker validation, and expanding clinical trials to bridge translational medicine gaps.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"596-605"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793685","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}

引用次数: 0

Genetics of ALS - genes and modifier. 肌萎缩性侧索硬化症基因及其修饰子的遗传学。

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-08-07 DOI: 10.1097/WCO.0000000000001416

Sonja Menge, Lorena Decker, Axel Freischmidt

{"title":"Genetics of ALS - genes and modifier.","authors":"Sonja Menge, Lorena Decker, Axel Freischmidt","doi":"10.1097/WCO.0000000000001416","DOIUrl":"10.1097/WCO.0000000000001416","url":null,"abstract":"Purpose of review: Amyotrophic lateral sclerosis (ALS) is a complex genetic disorder, and the pace of discoveries is very rapid. This review aims at briefly summarizing our current knowledge, and at discussing the progress of the last two years.Recent findings: Common variation in numerous genes and variants in some nuclear-encoded mitochondrial genes were linked to an increased or modified risk of ALS, respectively. Mitochondrial function, i.e. specific mitochondrial haplotypes and loss-of-function variants in mitochondria-related genes, was identified as potent modifier of ALS survival, but not risk. Pioneering analyses of copy number variations in ALS-related genes revealed an increased load in ALS, but causality is unclear. A rare hyperactive variant of ER stress associated transcription factor CREB3 was linked to both substantially decreased ALS risk and slower disease progression. Furthermore, variants in IGFBP7 were linked to rare \"ALS reversals\", but existence of such phenotypes is controversial.Summary: Common variation increasing ALS risk contributes to our understanding of sporadic ALS, and novel structural variants have the potential to at least partly explain the missing heritability in ALS. Identification of mitochondrial function and ER stress signaling as potent disease modifiers provide valuable starting points for therapeutic approaches beyond targeting single causative genes.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"568-573"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793686","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}

引用次数: 0

Antisense oligonucleotide therapy in amyotrophic lateral sclerosis. 反义寡核苷酸治疗肌萎缩性侧索硬化症。

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1097/WCO.0000000000001413

Gergo Erdi-Krausz, Pamela J Shaw

{"title":"Antisense oligonucleotide therapy in amyotrophic lateral sclerosis.","authors":"Gergo Erdi-Krausz, Pamela J Shaw","doi":"10.1097/WCO.0000000000001413","DOIUrl":"10.1097/WCO.0000000000001413","url":null,"abstract":"Purpose of review: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with few treatment options available. The approval of tofersen, an antisense oligonucleotide, for SOD1 -ALS by the FDA and EMA may herald a new era of treatment in these patients.Recent findings: So far, trials against the most common genetic form of ALS, C9orf72 , have been unsuccessful, but new preclinical data may show a promising new direction to take. Clinical trials targeting other, more rare genetic mutations associated with familial ALS are currently underway. Other research assessing the use of ASOs to target aberrant splicing associated with sporadic forms of ALS has also produced promising results in preclinical models, using patient-derived induced cellular models and animal models. These therapies are focussed largely on alleviating and reversing TDP-43 pathology, opening up the possibility of not only arresting disease progression, but reversing neurodegeneration.Summary: ASO therapies have made some promising steps towards treating familial ALS, particularly SOD1 . Ongoing early clinical/preclinical phase research is underway to utilise this technology in other genetic mutations linked with ALS, as well as in sporadic cases.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"574-580"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882404","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

Neurosyphilis in 2025: Erratum. 2025年的神经梅毒：勘误。

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-09-04 DOI: 10.1097/WCO.0000000000001409

引用次数: 0

Progress in ALS research 2025. ALS研究进展2025。

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-09-04 DOI: 10.1097/WCO.0000000000001410

Albert Ludolph

引用次数: 0

Inclusion body myositis - what are new lines of pathogenesis and therapy? 包涵体肌炎的发病机制和治疗有哪些新进展？

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-06-05 DOI: 10.1097/WCO.0000000000001393

Karsten Krause, Tobias Ruck, Felix Kleefeld

{"title":"Inclusion body myositis - what are new lines of pathogenesis and therapy?","authors":"Karsten Krause, Tobias Ruck, Felix Kleefeld","doi":"10.1097/WCO.0000000000001393","DOIUrl":"10.1097/WCO.0000000000001393","url":null,"abstract":"Purpose of review: Although inclusion body myositis (IBM) is considered a rare disease, it is the most prevalent inflammatory myopathy in adults over 50 years of age. Its complex pathophysiological background includes inflammatory and degenerative features, but it remains poorly understood. As a result, no effective therapy is currently available. In this review, we provide an update on the relevant contemporary literature addressing the clinical and pathophysiological aspects of IBM.Recent findings: Recent studies have investigated drugs for IBM, including the immunosuppressant sirolimus, but haven't shown satisfactory results. Some advancements have been made in investigating IBM pathophysiology: a cell culture model recapitulating key disease features has been established. Multiple studies have used RNA sequencing to elucidate disease-specific pathways, including selective type 2 fiber vulnerability. The importance of TDP-43 deposition and subsequent mis-splicing as a disease mechanism has been demonstrated. Further studies have shown the value of patient-reported outcome measures (PROM) and quantitative MRI as investigation tools. Research has also investigated and demonstrated the complex genetic susceptibility related to IBM.Summary: In conclusion, significant discoveries have been made in the past year that enhance our clinical and pathophysiological insights into IBM. Due to the persistent lack of effective therapeutic options, additional research is essential - not only to investigate potential treatments but also to reveal the disease's underlying mechanisms.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"546-550"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233488","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

Is amyotrophic lateral sclerosis less severe in mice than in humans? 肌萎缩性侧索硬化症在小鼠中的严重程度是否低于人类？

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1097/WCO.0000000000001412

Luc Dupuis, Janice Robertson

{"title":"Is amyotrophic lateral sclerosis less severe in mice than in humans?","authors":"Luc Dupuis, Janice Robertson","doi":"10.1097/WCO.0000000000001412","DOIUrl":"10.1097/WCO.0000000000001412","url":null,"abstract":"Purpose of review: We review here novel knock-in models of amyotrophic lateral sclerosis (ALS).Recent findings: Knock-in mouse models of various familial forms of ALS generally display a mild motor phenotype, with limited progression, that do not recapitulate the full-blown clinical picture of ALS.Summary: ALS is a devastating neurodegenerative disease in humans. Typically manifesting in the fifth or sixth decade of life, ALS leads to progressive motor dysfunction and death, usually within 2-5 years from symptom onset. A subset of ALS cases are dominantly inherited. Over the last 30 years, multiple mouse models of ALS have been generated, and recent advances in mouse genome editing techniques have enabled the generation of mouse strains carrying orthologous mutations in endogenous genes that mirror those causing familial forms of ALS. Intriguingly, many of these knock-in mouse models develop much milder phenotypes than patients with ALS carrying the same mutations. A full-blown ALS clinical phenotype seems to be only elicited upon overexpression of mutant genes beyond the endogenous levels. Here, we review these novel models and argue that these models could represent how ALS manifests in the mouse species. We also evaluate how these models could be used for characterizing mechanisms and preclinical drug evaluation.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"581-587"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788517","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

Neuromuscular sarcopenia: what do we know? 神经肌肉肌肉减少症：我们知道什么？

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-05-16 DOI: 10.1097/WCO.0000000000001373

Michael Drey

{"title":"Neuromuscular sarcopenia: what do we know?","authors":"Michael Drey","doi":"10.1097/WCO.0000000000001373","DOIUrl":"10.1097/WCO.0000000000001373","url":null,"abstract":"Purpose of review: Sarcopenia is a common and relevant health problem in the treatment of geriatric patients. After many years of dealing with the definition of this phenomenon, the focus in the future must be on underlying and treatable pathomechanisms.Recent findings: The article describes the initial state with regard to the definition of sarcopenia and derives from this the focus on subgroups of sarcopenia with treatable pathomechanisms. One subgroup of neuromuscular sarcopenia, which focuses on the degeneration of the neuromuscular junction, is discussed. In this context, the proteoglycan agrin with its ability to cluster acetylcholine receptors in the postsynaptic membrane of the muscle plays a role. Inactivation of agrin leads to destabilization of the neuromuscular junction and thus to sarcopenia. The resulting neuronal 22 kDa C-terminal agrin fragment should serve as a biomarker of neuromuscular sarcopenia.Summary: The neuronal C-terminal agrin fragment must be established as a biomarker for neuromuscular sarcopenia, taking renal function into account as the fragment accumulates in renal insufficient patients. On this basis, treatment with agrin could be a therapeutic option for this subgroup of sarcopenia.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"560-565"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076595","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

Recent progress in the molecular understanding and treatments of facioscapulohumeral muscular dystrophy. 面肩肱肌营养不良的分子认识与治疗进展。

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-06-05 DOI: 10.1097/WCO.0000000000001382

Roy Augustinus, Nicole Voet, Jessica C de Greef, Nicol C Voermans

{"title":"Recent progress in the molecular understanding and treatments of facioscapulohumeral muscular dystrophy.","authors":"Roy Augustinus, Nicole Voet, Jessica C de Greef, Nicol C Voermans","doi":"10.1097/WCO.0000000000001382","DOIUrl":"10.1097/WCO.0000000000001382","url":null,"abstract":"Purpose of review: Facioscapulohumeral muscular dystrophy (FSHD) is a progressive inherited myopathy, for which there is currently no cure available. This review focuses on the recent progress in the molecular understanding and treatments of FSHD.Recent findings: Recent studies on the molecular understanding of FSHD highlight its multifaceted complexity and suggest new targets for therapeutic intervention. Preclinical models, such as the 3D skeletal muscle, provide an easier way to study molecular pathways and serve as a platform for drug screenings. New insights on training and the new international guideline contribute to optimal symptomatic treatment. In parallel, research is advancing with generic and targeted molecular therapies aiming to inhibit DUX4 activity or its downstream effects.Summary: FSHD is caused by abnormal expression of the DUX4 gene. Our understanding of the molecular mechanisms underlying DUX4 and DUX4 target gene expression remains incomplete. However, advancements continue to clarify the roles of key proteins and genes, which might be of interest for future therapeutic therapies. Current therapies, treatments, and clinical trials for FSHD focus on molecular approaches, gene therapy, and symptom management. These developments indicate a growing focus on precision treatments and functional assessments, paving the way for improved FSHD management.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"504-512"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233490","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

Neurochemical biomarkers of amyotrophic lateral sclerosis: recent developments. 肌萎缩性侧索硬化症的神经化学生物标志物：最新进展。

IF 4.4 2区医学

Current Opinion in Neurology Pub Date : 2025-10-01 Epub Date: 2025-08-20 DOI: 10.1097/WCO.0000000000001411

Federico Verde

{"title":"Neurochemical biomarkers of amyotrophic lateral sclerosis: recent developments.","authors":"Federico Verde","doi":"10.1097/WCO.0000000000001411","DOIUrl":"10.1097/WCO.0000000000001411","url":null,"abstract":"Review purpose: To provide an overview of the recent developments in the field of neurochemical biomarkers of amyotrophic lateral sclerosis (ALS).Recent findings: Neurofilaments, especially NFL, have been confirmed to be good biomarkers for ALS. NFL may be diagnostically useful but its main role is as prognostic and pharmacodynamic biomarker. Inflammatory biomarkers, especially the chitinases, might also serve as pharmacodynamic biomarkers in treatment trials targeting neuroinflammation. GFAP could reflect cognitive-behavioural impairment. CSF dipeptides are diagnostic biomarkers for ALS caused by the C9ORF72 exanucleotide repeat expansion and may be used to confirm target engagement by experimental drugs. Levels of TDP-43 (virtually the ideal biomarker for ALS) in CSF and plasma have not been demonstrated to be consistently altered in ALS. However, promising advancements have been achieved in seed amplification assays for the protein, in its quantification in plasma extracellular vesicles, and in the measurement of CSF levels of a protein reflecting splicing dysfunction of TDP-43. Finally, blood phosphorylated tau has emerged as an ALS biomarker linked to lower motor neuron (or muscle) pathology.Summary: NFL is still the best neurochemical biomarker for ALS. However, substantial advances have been recently made, especially regarding detection of TDP-43 and blood phosphorylated tau.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"614-619"},"PeriodicalIF":4.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882405","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