Current Opinion in Neurology最新文献_第4页

Gene therapies for CMT neuropathies: from the bench to the clinic. 治疗 CMT 神经病的基因疗法：从实验室到临床。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-06-14 DOI: 10.1097/WCO.0000000000001289

Marina Stavrou, Kleopas A Kleopa

{"title":"Gene therapies for CMT neuropathies: from the bench to the clinic.","authors":"Marina Stavrou, Kleopas A Kleopa","doi":"10.1097/WCO.0000000000001289","DOIUrl":"10.1097/WCO.0000000000001289","url":null,"abstract":"Purpose of review: Charcot-Marie-Tooth (CMT) neuropathies are rare, genetically heterogeneous and progressive diseases for which there are no approved treatments and their management remains mostly supportive and symptomatic. This review is intended to provide an update on recent developments in gene therapies for different CMT neuropathies.Recent findings: Increasing knowledge of disease pathomechanisms underlying several CMT types has facilitated the development of promising viral and nonviral gene therapy approaches. Some of these therapies are currently approaching the crucial step of moving from the bench to the clinic, having passed the proof-of-concept stage in rodent models and some also in larger animals. However, questions of optimal delivery route and dose, off-target effects, and possible payload toxicity remain to be clarified for several of these approaches. Furthermore, limited resources, the rarity of most CMT subtypes, and issues of safety and regulatory requirements, create the need for consensus guidelines and optimal clinical trial design.Summary: Promising gene therapies have been developed for several CMT neuropathies, with proof-of-principle demonstrated in relevant disease models. Advantages and drawbacks of each approach are discussed and remaining challenges are highlighted. Furthermore, we suggest important parameters that should be considered in order to successfully translate them into the clinic.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"445-454"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317102","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

The genetics of amyotrophic lateral sclerosis. 肌萎缩性脊髓侧索硬化症的遗传学。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-08-22 DOI: 10.1097/WCO.0000000000001294

Melissa Nijs, Philip Van Damme

{"title":"The genetics of amyotrophic lateral sclerosis.","authors":"Melissa Nijs, Philip Van Damme","doi":"10.1097/WCO.0000000000001294","DOIUrl":"10.1097/WCO.0000000000001294","url":null,"abstract":"Purpose of review: Amyotrophic lateral sclerosis (ALS) has a strong genetic basis, but the genetic landscape of ALS appears to be complex. The purpose of this article is to review recent developments in the genetics of ALS.Recent findings: Large-scale genetic studies have uncovered more than 40 genes contributing to ALS susceptibility. Both rare variants with variable effect size and more common variants with small effect size have been identified. The most common ALS genes are C9orf72 , SOD1 , TARDBP and FUS . Some of the causative genes of ALS are shared with frontotemporal dementia, confirming the molecular link between both diseases. Access to diagnostic gene testing for ALS has to improve, as effective gene silencing therapies for some genetic subtypes of ALS are emerging, but there is no consensus about which genes to test for.Summary: Our knowledge about the genetic basis of ALS has improved and the first effective gene silencing therapies for specific genetic subtypes of ALS are underway. These therapeutic advances underline the need for better access to gene testing for people with ALS. Further research is needed to further map the genetic heterogeneity of ALS and to establish the best strategy for gene testing in a clinical setting.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"560-569"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533938","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

Current advance on distal myopathy genetics. 远端肌病遗传学的最新进展。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-07-16 DOI: 10.1097/WCO.0000000000001299

Johanna Ranta-Aho, Mridul Johari, Bjarne Udd

{"title":"Current advance on distal myopathy genetics.","authors":"Johanna Ranta-Aho, Mridul Johari, Bjarne Udd","doi":"10.1097/WCO.0000000000001299","DOIUrl":"10.1097/WCO.0000000000001299","url":null,"abstract":"Purpose of review: Distal myopathies are a clinically heterogenous group of rare, genetic muscle diseases, that present with weakness in hands and/or feet at onset. Some of these diseases remain accentuated in the distal muscles whereas others may later progress to the proximal muscles. In this review, the latest findings related to genetic and clinical features of distal myopathies are summarized.Recent findings: Variants in SMPX , DNAJB2, and HSPB6 have been identified as a novel cause of late-onset distal myopathy and neuromyopathy. In oculopharyngodistal myopathies, repeat expansions were identified in two novel disease-causing genes, RILPL1 and ABCD3. In multisystem proteinopathies, variants in HNRNPA1 and TARDBP , genes previously associated with amyotrophic lateral sclerosis, have been shown to cause late-onset distal myopathy without ALS. In ACTN2 -related distal myopathy, the first recessive forms of the disease have been described, adding it to the growing list of genes were both dominant and recessive forms of myopathy are present.Summary: The identification of novel distal myopathy genes and pathogenic variants contribute to our ability to provide a final molecular diagnosis to a larger number of patients and increase our overall understanding of distal myopathy genetics and pathology.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"515-522"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626268","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

The evolving spectrum of complex inherited neuropathies. 不断演变的复杂遗传性神经病谱。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-07-31 DOI: 10.1097/WCO.0000000000001307

Alexander M Rossor, Saif Haddad, Mary M Reilly

{"title":"The evolving spectrum of complex inherited neuropathies.","authors":"Alexander M Rossor, Saif Haddad, Mary M Reilly","doi":"10.1097/WCO.0000000000001307","DOIUrl":"10.1097/WCO.0000000000001307","url":null,"abstract":"Purpose of review: Inherited peripheral neuropathies can be divided into those diseases in which peripheral neuropathy is the sole or main feature of the disease (Charcot-Marie-Tooth disease) and those in which peripheral neuropathy is just one feature of a more complex syndrome. In recent years there has been a substantial expansion in the number of genes associated with complex neuropathy syndromes.Recent findings: This review will focus on emerging themes in this group of diseases, namely the increasing number of diseases due to repeat expansions; the emergence of both recessive and dominant negative alleles in the same gene producing a common phenotype and diseases in which there is selective loss of the allele from haematopoietic stem cells making genetic diagnosis on blood derived DNA problematic.Summary: In this review we provide a practical approach to investigating and diagnosing patients with peripheral neuropathy as part of a complex syndrome and provide an updated table of the genes associated with this group of diseases.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"427-444"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855053","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

Neuroinflammation in amyotrophic lateral sclerosis: pathogenic insights and therapeutic implications. 肌萎缩性脊髓侧索硬化症中的神经炎症：病因认识和治疗意义。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-05-22 DOI: 10.1097/WCO.0000000000001279

Aicee D Calma, Nathan Pavey, Parvathi Menon, Steve Vucic

{"title":"Neuroinflammation in amyotrophic lateral sclerosis: pathogenic insights and therapeutic implications.","authors":"Aicee D Calma, Nathan Pavey, Parvathi Menon, Steve Vucic","doi":"10.1097/WCO.0000000000001279","DOIUrl":"10.1097/WCO.0000000000001279","url":null,"abstract":"Purpose of review: Neuroinflammation appears to be an important pathogenic process in amyotrophic lateral sclerosis (ALS). Dysfunction of central immune pathways, including activation of microglia and astrocytes, and peripherally derived immune cells, initiate noncell autonomous inflammatory mechanisms leading to degeneration. Cell autonomous pathways linked to ALS genetic mutations have been recently identified as contributing mechanism for neurodegeneration. The current review provides insights into the pathogenic importance of central and peripheral inflammatory processes in ALS pathogenesis and appraises their potential as therapeutic targets.Recent findings: ALS is a multistep process mediated by a complex interaction of genetic, epigenetic, and environmental factors. Noncell autonomous inflammatory pathways contribute to neurodegeneration in ALS. Activation of microglia and astrocytes, along with central nervous system infiltration of peripherally derived pro-inflammatory innate (NK-cells/monocytes) and adaptive (cell-mediated/humoral) immune cells, are characteristic of ALS. Dysfunction of regulatory T-cells, elevation of pro-inflammatory cytokines and dysbiosis of gut microbiome towards a pro-inflammatory phenotype, have been reported as pathogenic mechanisms in ALS.Summary: Dysregulation of adaptive and innate immunity is pathogenic in ALS, being associated with greater disease burden, more rapid disease course and reduced survival. Strategies aimed at modulating the pro-inflammatory immune components could be of therapeutic utility.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"585-592"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075590","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 insights into haematology and peripheral nerve disease. 对血液学和周围神经疾病的最新见解。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-06-10 DOI: 10.1097/WCO.0000000000001291

Oliver Tomkins, Michael P Lunn

{"title":"Recent insights into haematology and peripheral nerve disease.","authors":"Oliver Tomkins, Michael P Lunn","doi":"10.1097/WCO.0000000000001291","DOIUrl":"10.1097/WCO.0000000000001291","url":null,"abstract":"Purpose of review: The association between clonal haematological disorders and peripheral nerve disease is recognized. Paraproteinaemic phenomena are the most common mechanism, but direct neural lymphomatous infiltration is seen and can be challenging to diagnose. Traditional and novel anticancer therapies have neuropathic side effects.Recent findings: Novel studies using sensitive techniques are refining the incidence of peripheral neuropathy in patients with a monoclonal gammopathy, and the pathogenesis of IgM Peripheral neuropathy (PN) and POEMS syndrome. Recent series give insight into the characteristics and diagnostic challenges of patients with neurolymphomatosis and amyloid light chain amyloidosis. There is an increasing repertoire of effective anticancer drugs in haematological oncology, but chemotherapy-related neuropathy remains a common side effect.Summary: This review of the current literature focuses on recent updates and developments for the paraproteinaemic neuropathies, and the evaluation, diagnosis and treatment of peripheral nerve disease due to high-grade and low-grade lymphomas and lymphoproliferative disorders.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"461-466"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300296","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

Congenital myasthenic syndromes: increasingly complex. 先天性肌无力综合征：日益复杂。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-07-25 DOI: 10.1097/WCO.0000000000001300

Sithara Ramdas, David Beeson, Yin Yao Dong

{"title":"Congenital myasthenic syndromes: increasingly complex.","authors":"Sithara Ramdas, David Beeson, Yin Yao Dong","doi":"10.1097/WCO.0000000000001300","DOIUrl":"10.1097/WCO.0000000000001300","url":null,"abstract":"Purpose of review: Congenital myasthenia syndromes (CMS) are treatable, inherited disorders affecting neuromuscular transmission. We highlight that the involvement of an increasing number of proteins is making the understanding of the disease mechanisms and potential treatments progressively more complex.Recent findings: Although early studies identified mutations of proteins directly involved in synaptic transmission at the neuromuscular junction, recently, next-generation sequencing has facilitated the identification of many novel mutations in genes that encode proteins that have a far wider expression profile, some even ubiquitously expressed, but whose defective function leads to impaired neuromuscular transmission. Unsurprisingly, mutations in these genes often causes a wider phenotypic disease spectrum where defective neuromuscular transmission forms only one component. This has implications for the management of CMS patients.Summary: Given the widening nonneuromuscular junction phenotypes in the newly identified forms of CMS, new therapies need to include disease-modifying approaches that address not only neuromuscular weakness but also the multisystem involvement. Whilst the current treatments for CMS are highly effective for many subtypes there remains, in a proportion of CMS patients, an unmet need for more efficacious therapies.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"493-501"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757702","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

Muscle ultrasound in myopathies. 肌病中的肌肉超声。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-07-25 DOI: 10.1097/WCO.0000000000001306

Alex Vicino, Dimitra Veltsista, Nens van Alfen

{"title":"Muscle ultrasound in myopathies.","authors":"Alex Vicino, Dimitra Veltsista, Nens van Alfen","doi":"10.1097/WCO.0000000000001306","DOIUrl":"10.1097/WCO.0000000000001306","url":null,"abstract":"Purpose of review: This review highlights recent developments in the field of muscle ultrasound (MUS) for the diagnosis and follow up of muscle disorders.Recent findings: The diagnostic screening capacity of quantitative grayscale analysis is still sufficient to assess children suspected of a neuromuscular disorder. A combination of visual and quantitative assessment is advised for optimal interpretation. MUS was more sensitive but less specific than MRI for detecting pathology in limb girdle dystrophies and inflammatory myopathies. New techniques such as shearwave elastography and artificial intelligence algorithms for automated image segmentation show promise but need further development for use in everyday practice.Muscle ultrasound has high correlations with clinical measures of function in skeletal and respiratory muscles and the orofacial region, in most of the myopathies and dystrophies studied. Over time, imaging changes precede changes in clinical status, making them attractive for biomarker use in trials. In Duchenne muscular dystrophy MUS was also responsive to the effects of steroid treatment.Summary: Muscle ultrasound is a sensitive technique to diagnose and follow up of skeletal, facial and respiratory muscles in neuromuscular disorders. Its role is both complementary to and partially overlapping with that of MRI.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"549-557"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757704","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

Emerging concepts and therapies for amyotrophic lateral sclerosis. 肌萎缩性脊髓侧索硬化症的新概念和疗法。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-09-05 DOI: 10.1097/WCO.0000000000001308

Matthew C Kiernan, Ryuji Kaji

引用次数: 0

Obesity-related neuropathy: the new epidemic. 肥胖相关神经病：新的流行病。

IF 4.1 2区医学

Current Opinion in Neurology Pub Date : 2024-10-01 Epub Date: 2024-06-12 DOI: 10.1097/WCO.0000000000001292

Melissa A Elafros, Evan Lee Reynolds, Brian C Callaghan

{"title":"Obesity-related neuropathy: the new epidemic.","authors":"Melissa A Elafros, Evan Lee Reynolds, Brian C Callaghan","doi":"10.1097/WCO.0000000000001292","DOIUrl":"10.1097/WCO.0000000000001292","url":null,"abstract":"Purpose of review: To examine the evidence evaluating the association between obesity and neuropathy as well as potential interventions.Recent findings: Although diabetes has long been associated with neuropathy, additional metabolic syndrome components, including obesity, are increasingly linked to neuropathy development, regardless of glycemic status. Preclinical rodent models as well as clinical studies are shedding light on the mechanisms of obesity-related neuropathy as well as challenges associated with slowing progression. Dietary and surgical weight loss and exercise interventions are promising, but more data is needed.Summary: High-fat-diet rodent models have shown that obesity-related neuropathy is a product of excess glucose and lipid accumulation leading to inflammation and cell death. Clinical studies consistently demonstrate obesity is independently associated with neuropathy; therefore, likely a causal risk factor. Dietary weight loss improves neuropathy symptoms but not examination scores. Bariatric surgery and exercise are promising interventions, but larger, more rigorous studies are needed. Further research is also needed to determine the utility of weight loss medications and ideal timing for obesity interventions to prevent neuropathy.","PeriodicalId":11059,"journal":{"name":"Current Opinion in Neurology","volume":" ","pages":"467-477"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305647","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