Neurotherapeutics最新文献_第10页

Clinical decision making around commercial use of gene and genetic therapies for spinal muscular atrophy 围绕脊髓性肌萎缩症基因和遗传疗法的商业用途进行临床决策。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00437

Megan A. Waldrop

引用次数: 0

Immune responses to central nervous system directed adeno-associated virus gene therapy: Does direct CNS delivery make a difference? 中枢神经系统定向腺相关病毒基因疗法的免疫反应：直接向中枢神经系统递送是否会产生影响？

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00435

Ashley L. Harkins , Prajakta P. Ambegaokar , Allison M. Keeler

{"title":"Immune responses to central nervous system directed adeno-associated virus gene therapy: Does direct CNS delivery make a difference?","authors":"Ashley L. Harkins , Prajakta P. Ambegaokar , Allison M. Keeler","doi":"10.1016/j.neurot.2024.e00435","DOIUrl":"10.1016/j.neurot.2024.e00435","url":null,"abstract":"<div><p>Adeno-associated virus (AAV) mediated gene therapy is a leading gene delivery platform with potential to transform the landscape of treatment for neurological disorders. While AAV is deemed non-immunogenic compared to other viral vectors, adverse immune reactions have been observed in the clinic, raising concerns. As the central nervous system (CNS) has a tightly regulated immune system, characterized by a degree of tolerance, it has been considered a unique target for AAV gene therapy. AAV vectors have shown promising results for the treatment of several CNS disorders including Spinal Muscular Atrophy, Giant Axonal Neuropathy, Amyotrophic Lateral Sclerosis, Tay Sachs Disease, Parkinson's Disease, and others, demonstrating safety and success. The Food and Drug Administration (FDA) approval of Zolgensma and European Medicines Agency (EMA) approval of Upstaza, for Spinal Muscular Atrophy (SMA) and Aromatic <span>l</span>-amino acid decarboxylase deficiency (AADC) respectively, represent this success, all while highlighting significant differences in immune responses to AAV, particularly with regards to therapeutic administration route. AAV therapies like Upstaza that are injected directly into the immune-specialized brain have been characterized by mild immune response profiles and minor adverse events, whereas therapies like Zolgensma that are injected systemically demonstrate more robust immune stimulation and off-target toxicities. Despite these contrasting parallels, these therapeutics and others in the clinic have demonstrated clinical benefit for patients, warranting further exploration of immune responses to CNS-directed AAV clinical trials. Thus, in this review, we discuss effects of different routes of AAV administration on eliciting local and peripheral immune responses specifically observed in CNS-targeted trials.</p></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1878747924001211/pdfft?md5=b4ab2a6edee35de43bb985ec09d50c68&pid=1-s2.0-S1878747924001211-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048047","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

Novel Mitochondrial Protective Agent for Parkinson’s Disease Targeting the PINK1/LRRK2 Axis 以 PINK1/LRRK2 轴为靶点治疗帕金森病的新型线粒体保护剂

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00416

Sherine S. Chan Ph.D. , Emmaline Bendell B.A. , Jesse McClure M.D., Ph.D., Pharm.D. , James Chou Ph.D.

引用次数: 0

Human Endogenous Retrovirus-K (HERV-K) env Knockdown by AAV9-mediated shRNA Attenuates Amyotrophic Lateral Sclerosis (ALS)-like Symptoms in Transgenic Mice 通过 AAV9 介导的 shRNA 敲除人类内源性逆转录病毒-K (HERV-K) env 可减轻转基因小鼠的肌萎缩性脊髓侧索硬化症 (ALS) 症状

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00412

Myoung-Hwa Lee Ph.D., Wenxue Li Ph.D., Kevon Sampson M.A., Melina Jones Ph.D., Joseph Steiner Ph.D., Avindra Nath M.D.

引用次数: 0

Antisense Oligonucleotides Directed Against a Human Endogenous Retrovirus for Treatment of Amyotrophic Lateral Sclerosis 针对人类内源性逆转录病毒的反义寡核苷酸用于治疗肌萎缩侧索硬化症

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00399

Kevon Sampson M.S., Wenxue Li Ph.D., Myoung Hwa Lee Ph.D., Lisa Henderson Ph.D., Avindra Nath M.D.

引用次数: 0

Pharmacological modulation of inflammatory oligodendrocyte progenitor cells using three multiple sclerosis disease modifying therapies in vitro 在体外使用三种多发性硬化症疾病调节疗法对炎性少突胶质祖细胞进行药理调节。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00379

Larissa Jank , Riley B. Catenacci , Veronica Minney , Danny Galleguillos , Peter A. Calabresi

{"title":"Pharmacological modulation of inflammatory oligodendrocyte progenitor cells using three multiple sclerosis disease modifying therapies in vitro","authors":"Larissa Jank , Riley B. Catenacci , Veronica Minney , Danny Galleguillos , Peter A. Calabresi","doi":"10.1016/j.neurot.2024.e00379","DOIUrl":"10.1016/j.neurot.2024.e00379","url":null,"abstract":"<div><p>Preclinical studies of pro-remyelinating therapies for multiple sclerosis tend to neglect the effect of the disease-relevant inflammatory milieu. Interferon-gamma (IFN-γ) is known to suppress oligodendrocyte progenitor cell (OPC) differentiation and induce a recently described immune OPC (iOPC) phenotype characterized by expression of major histocompatibility complex (MHC) molecules. We tested the effects of cladribine (CDB), dimethylfumarate (DMF), and interferon-beta (IFN-β), existing anti-inflammatory therapies for MS, on the IFN-γ-induced iOPC formation and OPC differentiation block. In line with previous reports, we demonstrate that IFN-β and DMF inhibit OPC proliferation, while CDB had no effect. None of the drugs exhibited cytotoxic effects at the physiological concentrations tested <em>in vitro.</em> In a differentiation assay, none of the drugs were able to promote differentiation, under inflammatory or basal conditions. To study drug effects on iOPCs, we monitored MHC expression <em>in vitro</em> with live cell imaging using cells isolated from MHC reporter mice. IFN-β suppressed induction of MHC class II, and DMF led to suppression of both class I and II. CDB had no effect on MHC induction. We conclude that promoting proliferation and differentiation and suppressing iOPC induction under inflammatory conditions may require separate therapeutic strategies and must be balanced for maximal repair. Our <em>in vitro</em> MHC screening assay can be leveraged across cell types to test the effects of drug candidates and disease-related stimuli.</p></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1878747924000655/pdfft?md5=e98c2b091876f393391c13a666912f10&pid=1-s2.0-S1878747924000655-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154929","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

Advances in diagnosis and treatment of vestibular migraine and the vestibular disorders it mimics 前庭性偏头痛及其模拟的前庭疾病的诊断和治疗进展。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00381

Nicholas E.F. Hac , Daniel R. Gold

{"title":"Advances in diagnosis and treatment of vestibular migraine and the vestibular disorders it mimics","authors":"Nicholas E.F. Hac , Daniel R. Gold","doi":"10.1016/j.neurot.2024.e00381","DOIUrl":"10.1016/j.neurot.2024.e00381","url":null,"abstract":"<div><p>Dizziness is one of the most common chief complaints in both the ambulatory care setting and the emergency department. These symptoms may be representative of a broad range of entities. Therefore, any attempt at treatment must first start with determining the etiology. In this current perspective, we focus specifically on the diagnosis of and treatment of vestibular migraine, which is common and overlaps clinically with a variety of other diagnoses. We discuss the traditional treatments for vestibular migraine in addition to the recent explosion of novel migraine therapeutics. Because vestibular migraine can mimic, or co-exist with, a variety of other vestibular diseases, we discuss several of these disorders including persistent postural-perceptual dizziness, benign paroxysmal positional vertigo, post-concussive syndrome, Ménière's disease, and cerebrovascular etiologies. We discuss the diagnosis of each, as well as overlapping and distinguishing clinical features of which the reader should be aware. Finally, we conclude with evidence based as well as expert commentary on management, with a particular emphasis on vestibular migraine.</p></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1878747924000679/pdfft?md5=c0618a7d49b6895125b328ce5d1970c9&pid=1-s2.0-S1878747924000679-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284356","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

Electroacupuncture improves gastrointestinal motility through a central-cholinergic pathway-mediated GDNF releasing from intestinal glial cells to protect intestinal neurons in Parkinson's disease rats 电针通过中枢胆碱能通路介导的肠胶质细胞释放GDNF来改善帕金森病大鼠的胃肠道运动，从而保护肠神经元。

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00369

{"title":"Electroacupuncture improves gastrointestinal motility through a central-cholinergic pathway-mediated GDNF releasing from intestinal glial cells to protect intestinal neurons in Parkinson's disease rats","authors":"","doi":"10.1016/j.neurot.2024.e00369","DOIUrl":"10.1016/j.neurot.2024.e00369","url":null,"abstract":"<div><p>Constipation symptoms of Parkinson's disease (PD) seriously reduce the quality of life of patients and aggravate the development of the disease, but current treatment options still cannot alleviate the progress of constipation. Electroacupuncture (EA) is a new method for the treatment of constipation, which can effectively treat the symptoms of constipation in PD patients. However, the specific regulatory mechanisms of EA in the treatment of constipation symptoms in PD remain unclear. The aim of this study is to investigate the therapeutic effect of EA on PD constipation rats and its regulatory mechanism. A rotenone (ROT)-induced gastrointestinal motility disorder model was used to simulate the pathological process of constipation in PD. The results showed that EA could effectively promote gastrointestinal peristalsis, reduce α-synuclein accumulation in substantia nigra and colon and colonic injury in rats after ROT administration. Mechanistically, EA activation of the central-cholinergic pathway increases acetylcholine release in the colon. At the same time, EA up-regulated the co-expression of enteric glial cells (EGCs) and α7 nicotinic acetylcholine receptor (α7nAChR). EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats. Further mechanistic studies showed that EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues. The present study confirmed that EA upregulates α7nAChR through a central-cholinergic mechanism to promote GDNF release from EGCs, thereby protecting intestinal neurons and thereby improving gastrointestinal motility.</p></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1878747924000552/pdfft?md5=df876400aaeddf68c8c60dbff5e9ef1c&pid=1-s2.0-S1878747924000552-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922019","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

BHV-7000, A Novel, Selective Kv7.2/7.3 Potassium Channel Activator, Demonstrates Dose-Dependent Pharmacodynamic Effects on EEG Parameters in Healthy Adults 新型选择性 Kv7.2/7.3 钾通道激活剂 BHV-7000 对健康成人脑电图参数的药效学效应呈剂量依赖性

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00402

Jason Lerner M.D. , Bharat Awsare M.D. , Heather Sevinsky M.S. , Eric Ashbrenner M.S. , Randall Killingsworth B.A. , Racheal Kendrick PharmD , Emiel Vereycken M.S. , Nigel Colenbier Ph.D. , Caroline Neuray M.D. , Pieter van Mierlo Ph.D. , Jeremy Slater M.D. , David Wyatt M.D. , Irfan Qureshi M.D. , Steven Dworetzky Ph.D. , Michael Bozik M.D.

引用次数: 0

Gene therapy for neurologic disorders 神经系统疾病的基因疗法

IF 5.6 2区医学

Neurotherapeutics Pub Date : 2024-07-01 DOI: 10.1016/j.neurot.2024.e00453

Florian S. Eichler, Robert H. Brown Jr.

引用次数: 0