Neurotherapeutics最新文献

{"title":"Nose-to-brain delivery of a SOD1-stabilizing small molecule ameliorates pathology in an ALS mouse model","authors":"Ranjithkumar Dhandapani ,&nbsp;Shamchal Bakavayev ,&nbsp;Anna Armoza ,&nbsp;Marina Bersudsky ,&nbsp;Arina Shlifer ,&nbsp;Galit Yehezkel ,&nbsp;Alexandra Tsitrina ,&nbsp;Zeev Barak ,&nbsp;Amnon C. Sintov ,&nbsp;Stanislav Engel","doi":"10.1016/j.neurot.2026.e00904","DOIUrl":"10.1016/j.neurot.2026.e00904","url":null,"abstract":"<div><div>Exposure of a pathogenic β6/β7 loop neo-epitope has been proposed to contribute to the pathogenesis of misfolded Cu/Zn superoxide dismutase (SOD1) in amyotrophic lateral sclerosis (ALS) by mediating early events in its noxious structural transformation and prion-like activity. Antibody-mediated blockade of this epitope was shown to ameliorate disease phenotype in an ALS animal model. Here, as an alternative strategy, we sought to block this epitope using a small molecule designed to occupy the inter-subunit cavity framed by the two β6/β7 loops. Using a structure-based virtual screen targeting this cavity, we identified a small molecule, N-[3-(3-methylimidazo[2,1-b][1,3]thiazol-6-yl)phenyl]-4-sulfamoylbenzamide (C7), that preferentially bound the native-like conformation of SOD1, reduced β6/β7 loop epitope accessibility, and inhibited irreversible apo-SOD1 misfolding in vitro. Delivered to presymptomatic hSOD1^G93A mice via a nanoparticle-based nose-to-brain delivery system, C7 significantly delayed the onset of motor abnormalities and modestly extended survival. At disease onset, spinal cord analysis revealed reduced misfolded SOD1 inclusions and attenuated astro- and microgliosis. Analysis of C7 concentrations in combined brain and spinal cord tissue indicated rapid but saturable nose-to-CNS uptake and slow clearance. Our findings demonstrate that targeting the surface cavity shaped by the β6/β7 loops of SOD1 with a reversibly-binding small molecule can ameliorate ALS-like disease <em>in vivo</em>, potentially by counteracting early misfolding events and/or limiting prion-like propagation of molecular pathology. However, saturable nose-to-CNS uptake of C7 restricts CNS exposure and likely constrains therapeutic efficacy, underscoring the need to define the rate-limiting pharmacokinetic step and to optimize the nanoparticle formulation and/or physicochemical properties of the C7 scaffold.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 3","pages":"Article e00904"},"PeriodicalIF":6.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675323","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}

{"title":"Intermittent theta-burst stimulation to enhance physical therapy in Parkinson's disease: The STEP-PD randomized trial","authors":"Hong-yu Zhang ,&nbsp;Ting-ting Hou ,&nbsp;Ke-ke Chen ,&nbsp;Tian Zhang ,&nbsp;Yi-heng Wang ,&nbsp;Yi-xuan Wang ,&nbsp;De-tao Meng ,&nbsp;Zhen-zhen Li ,&nbsp;Hong-jiao Yan ,&nbsp;Yi Zhen ,&nbsp;Xia An ,&nbsp;Rui-dan Wang ,&nbsp;Jin-ping Fang ,&nbsp;Yong-hong Liu ,&nbsp;Wen-jun Du ,&nbsp;Jia Du ,&nbsp;Ping Wang ,&nbsp;Yan-jun Liu ,&nbsp;Xiao-yan Yan ,&nbsp;Bastiaan R. Bloem ,&nbsp;Bo-yan Fang","doi":"10.1016/j.neurot.2026.e00897","DOIUrl":"10.1016/j.neurot.2026.e00897","url":null,"abstract":"<div><div>Physical therapy (PT) is commonly used to alleviate specific symptoms of Parkinson's disease (PD). Its efficacy may be enhanced by cortical priming, which aims to improve the brain's responsiveness to rehabilitation. This randomized, double-blind, sham-controlled trial—Stimulation to Enhance Physical Therapy in Parkinson's Disease (STEP-PD)—investigated whether combining PT with intermittent theta-burst stimulation (iTBS) applied over the primary motor cortex (M1-iTBS) could provide additional gains in motor function in patients with PD. Fifty participants with PD received PT combined with either bilateral M1-iTBS or sham-iTBS, twice daily, five days per week for two weeks. The primary outcome was the change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) in the OFF-medication state, assessed at baseline and immediately post-intervention. Secondary outcomes included the Parkinson's Disease Questionnaire-39 (PDQ-39), and exploratory outcomes included clinical and instrumented assessments of gait and balance, as well as electroencephalography (EEG)-based measures of functional connectivity. Patients receiving PT combined with M1-iTBS showed greater acute improvement in OFF-state MDS-UPDRS III scores compared to those receiving sham stimulation (Δ = −4.60, <em>p</em> = 0.034). There were no significant differences in PDQ-39 scores. Exploratory analyses revealed improved gait stability, fewer falls, and reduced beta-band synchronization on resting-state EEG, suggesting that M1-iTBS may modulate motor networks to facilitate functional recovery. These findings suggest that combining PT with M1-iTBS has promise as an acute cortical priming approach to improve the short-term efficacy of PD rehabilitation, although further research is required to determine the sustainability of these effects.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 3","pages":"Article e00897"},"PeriodicalIF":6.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147601993","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}

{"title":"Neuronal alkaline phosphatase promotes the spread of Tau-induced pathology, and its blockade prevents neurodegeneration and memory loss","authors":"Lucía Soria-Tobar ,&nbsp;Daniel Ouro-Corredera ,&nbsp;Laura Roman-Valero ,&nbsp;Félix Hernández ,&nbsp;José Luis Millán ,&nbsp;Beatriz Álvarez-Castelao ,&nbsp;Álvaro Sebastián-Serrano ,&nbsp;Paloma Aivar ,&nbsp;Miguel Díaz-Hernández","doi":"10.1016/j.neurot.2026.e00869","DOIUrl":"10.1016/j.neurot.2026.e00869","url":null,"abstract":"<div><div>Tauopathies, such as Alzheimer's disease (AD), are neurodegenerative disorders marked by abnormal intraneuronal aggregates of phosphorylated Tau protein. Unfortunately, no effective treatment is currently available. Since extracellular Tau (eTau) is essential for the spread of cerebral tauopathy, immunotherapy approaches using specific antibodies against Tau have been investigated. However, these strategies have shown limited applicability and benefit. Because previous in vitro studies reported that dephosphorylation of eTau by tissue-nonspecific alkaline phosphatase (TNAP) enhances its neurotoxicity, here we evaluate how neuronal TNAP contributes to Tau-induced neurotoxicity in vivo. To address this, we generated new transgenic mouse lines using Cre-lox technology to i) specifically delete TNAP in excitatory neurons of P301S mice, a well-characterized tauopathy model, or ii) induce neuronal TNAP overexpression in WT mice. Moreover, we compare the in vivo spreading capacity of phospho-eTau and dephospho-eTau-induced neurotoxicity. Our findings show that neuronal TNAP deletion in P301S mice reduces i) neuronal and synaptic loss, ii) the number of neurons with neurofibrillary tangles (NFTs), iii) reactive astrogliosis and microgliosis, and iv) brain calcifications; collectively, these changes lead to v) improved memory function in these mice. Conversely, overexpression of neuronal TNAP in WT mice alone is sufficient to cause i) loss of thalamic neurons and synaptic contacts, ii) formation of intracellular NFTs, iii) reactive gliosis, iv) brain calcifications, and v) memory impairment. These results demonstrate that neuronal TNAP promotes Tau-induced neurotoxicity spreading by facilitating eTau dephosphorylation, which confirms this ectoenzyme as a promising therapeutic target for tauopathies.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 2","pages":"Article e00869"},"PeriodicalIF":6.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453112","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}

{"title":"Longitudinal multi-omics profiling of spinal muscular atrophy","authors":"Ivana Dabaj ,&nbsp;Thi Hai Yen Nguyen ,&nbsp;Emmanuelle Lagrue ,&nbsp;Franklin Ducatez ,&nbsp;Stéphane Allouche ,&nbsp;Jérôme Ausseil ,&nbsp;Andreea Seferian ,&nbsp;Marta Gomez - Garcia de la Banda ,&nbsp;Audrey Benezit ,&nbsp;Aurélie Phelep ,&nbsp;Mondher Chouchane ,&nbsp;Stéphane Vasseur ,&nbsp;Maud Chapart ,&nbsp;Stéphane Marret ,&nbsp;Susana Quijano Roy ,&nbsp;Abdellah Tebani ,&nbsp;Soumeya Bekri","doi":"10.1016/j.neurot.2026.e00880","DOIUrl":"10.1016/j.neurot.2026.e00880","url":null,"abstract":"<div><div>Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by <em>SMN1</em> gene variants, leading to the degeneration of anterior horn cells in the spinal cord. It is a disabling disease with varying severity. Nusinersen, the first approved in France, has dramatically transformed SMA management. However, the significant variability in patient response and disease progression highlights a critical need for objective, measurable indicators. This study aims to identify biomarkers in cerebrospinal fluid (CSF) and plasma associated with the clinical status of treatment-naive patients and their disease progression during therapy. We performed targeted metabolomics and proteomics analyses on plasma and CSF samples from SMA patients before and after six months of treatment, along with controls. The differential analysis was carried out to discover the SMA biomarkers. We found that levels of acylcarnitines, biogenic amines, and neurology-related proteins were mainly elevated, while glycerophospholipids primarily decreased in SMA plasma samples compared to controls. The biomarkers showed good performance in distinguishing SMA from controls with plasma AUCs &gt;0.9. NEFH and creatinine were among the most prominent biomarkers for SMA diagnosis. Besides, 26 neurology-related proteins were found to be altered in patient CSF compared to controls. Furthermore, 11 potential proteins were identified to distinguish patients with 2 copies of <em>SMN2</em> from those with 3 or 4 copies using plasma. By unveiling specific biomarkers, this study offers valuable insights for accurate disease diagnosis and monitoring treatment effectiveness. This enables personalized SMA management and accelerates the development of targeted therapies.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 2","pages":"Article e00880"},"PeriodicalIF":6.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453109","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}

{"title":"Lafora disease gene therapy: EPM2A but not EPM2B overexpression results in Lafora body formation","authors":"Esther O. Alao ,&nbsp;Mehrnaz Sheibani ,&nbsp;Jun Wu ,&nbsp;Ummay Marriam ,&nbsp;Doretha Evans ,&nbsp;Sahba Kasiri ,&nbsp;Mayank Verma ,&nbsp;Silvia Nitschke ,&nbsp;Felix Nitschke ,&nbsp;Steven J. Gray ,&nbsp;Sharmistha Mitra ,&nbsp;Berge A. Minassian","doi":"10.1016/j.neurot.2026.e00866","DOIUrl":"10.1016/j.neurot.2026.e00866","url":null,"abstract":"<div><div>Lafora disease (LD) is a fatal teenage-onset neurodegenerative epilepsy caused by loss-of-function mutations of the genes encoding the laforin phosphatase-malin E3 ubiquitin ligase complex. This complex regulates glycogen structural integrity, through yet unclear mechanisms. Deficiencies of the complex lead few glycogen molecules at a time to misshape, precipitate and cumulate into toxic Lafora bodies (LBs) that drive LD. We developed an intrathecal AAV9-based gene therapy for malin-deficient LD and obtained preclinical efficacy without toxicity. A similar gene therapy for laforin-deficient LD also afforded efficacy, but with a relatively narrow therapeutic window. When overexpressed, laforin paradoxically led to LB generation and did so at a rate higher than in LD. The phenomenon was invariably observed first and dominantly in dorsal root ganglia (DRG) and occurred irrespective of where in the CSF axis the viral vector was delivered. Laforin overexpression-mediated LB formation represents novel biology, which we characterize and show that it occurs independently of laforin and malin's enzymatic activities. The accumulations are time-dependent, which toward clinical development will necessitate longer preclinical and clinical safety monitoring. The effect is strongest with species mismatch (i.e., expression of human laforin in mice), which may require matched-species preclinical development. Finally, the DRG are sentinel, and their pathology and neurophysiology can serve to monitor the iatrogenic toxicity. Our work suggests a clear gene therapy development path for malin-deficient LD, and sets important guardrails for gene therapy for laforin-dependent LD. It also opens a new avenue to understanding the basic biologies of glycogen quality control and LD.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 2","pages":"Article e00866"},"PeriodicalIF":6.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453104","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}

{"title":"Altered Erythrocyte Function via TLR9-ox-mtDNA Binding Links Mitochondrial Oxidative Damage to Systemic Inflammation in Multiple Sclerosis","authors":"Lingfei Yang ,&nbsp;Qianmeng Hao ,&nbsp;Yufei Chen ,&nbsp;Yudi Xu ,&nbsp;Ziyi Chen ,&nbsp;Qingsheng Li ,&nbsp;Yaobing Yao ,&nbsp;Zhe Gong ,&nbsp;Huimin Liu ,&nbsp;Hongzhuo Qin ,&nbsp;Yanfei Li ,&nbsp;Yanjie Jia","doi":"10.1016/j.neurot.2026.e00863","DOIUrl":"10.1016/j.neurot.2026.e00863","url":null,"abstract":"<div><div>Multiple sclerosis (MS), an autoimmune disorder of the central nervous system(CNS), is charactered by neuroinflammation and neurodegeneration. Red blood cells (RBCs) are the most abundant cells in circulation, yet their immunological roles remain poorly understood, especially in neuroimmunology. Here, we explored the role and mechanism of erythrocytes in linking CNS pathology to systemic inflammation in MS, by combining clinical epidemiology and experimental model validation. In UK Biobank (1,056 MS patients; 501,314 controls), MS patients exhibited significantly altered erythrocyte function. Notably, lower baseline erythrocyte counts were inversely associated with MS incidence. Our clinical cohort of 110 relapsing-remitting MS (RRMS) patients revealed progressive declines in RBC parameters (RBC counts, hemoglobin, hematocrit) which associated with disease duration and worse EDSS scores. In RRMS patients, RBCs proteomics and flow cytometry revealed TLR9 membrane translocation and CD47 downregulation. Ox-mtDNA-bound erythrocytes were more phagocytosed by macrophages, which subsequently triggered inflammatory activation and type I interferon responses. These findings were corroborated in the EAE model, where CNS-derived ox-mtDNA was found bound to erythrocyte TLR9, accompanied by compensatory erythropoiesis and interferon-β-driven inflammation. Treatment with the mitochondrial-targeted antioxidant MitoQ effectively normalized erythrocyte TLR9/CD47 expression, reduced ox-mtDNA release, and alleviated neuroinflammation. Collectively, our work defines a novel erythrocyte-TLR9-ox-mtDNA axis that links CNS mitochondrial damage to peripheral inflammation in MS. By integrating clinical cohort data with proteomics and experimental models, we establish erythrocyte pathology as a central feature of MS and highlight the therapeutic potential of targeting mitochondrial dysfunction to disrupt this cascade.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 2","pages":"Article e00863"},"PeriodicalIF":6.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453106","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}

{"title":"Test-retest reliability and symptom association of personalized depression TMS targets: A comparative study of refined seed-based (RSA) and hierarchical clustering (HCA) approaches","authors":"Hui Zhou ,&nbsp;Yanmeng Bao ,&nbsp;Jiasheng Xu ,&nbsp;Dan Wang ,&nbsp;Fengji Geng ,&nbsp;Wanjun Guo ,&nbsp;Yuzheng Hu","doi":"10.1016/j.neurot.2026.e00884","DOIUrl":"10.1016/j.neurot.2026.e00884","url":null,"abstract":"<div><div>Personalized transcranial magnetic stimulation (TMS) targeting holds promise for improving depression treatment, but its clinical translation is hindered by limited open-source implementation and systematic comparisons of target reproducibility and clinical relevance. We implemented two leading personalized TMS-target generating approaches, namely refined seed-based (RSA) and hierarchical clustering (HCA) algorithms, and compared them on (1) test-retest reliability of derived targets, and (2) association of target-sgACC connectivity with depressive symptoms. Using resting-state fMRI data from healthy and depressed individuals, spatial reliability was quantified via inter-run Euclidean distances, and clinical relevance was assessed through correlations between depression severity and functional connectivity of targets with sgACC. Effects of global signal regression (GSR) were also evaluated. The results showed that RSA produced targets in more superior and postrior part of DLPFC and demonstrated significantly higher test-retest reliability than HCA (smaller inter-run Euclidean distances). Further, RSA-derived target-sgACC connectivity correlated positively with depression severity, which was absent in HCA-derived targets. In addition, GSR improved spatial reliability for RSA but not HCA. Our results indicate that RSA exhibits superior test-retest reliability and symptom association compared to HCA, yet large-scale clinical trials are warranted to determine which approach yields superior therapeutic efficacy, and open-sourced implementation may accelerate clinical adoption.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 2","pages":"Article e00884"},"PeriodicalIF":6.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453110","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}

{"title":"Focussed ultrasound thalamotomy and functional MRI as windows to neural networks underlying essential tremor","authors":"Stephen Tisch","doi":"10.1016/j.neurot.2026.e00893","DOIUrl":"10.1016/j.neurot.2026.e00893","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 2","pages":"Article e00893"},"PeriodicalIF":6.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574566","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}

{"title":"Diabetes mellitus and efficacy of dual antiplatelet in acute ischemic stroke: A post hoc analysis of the ATAMIS trial","authors":"Xiao-Wen Hou ,&nbsp;Yu Cui ,&nbsp;Hong-Ting Yan ,&nbsp;Fei Liu ,&nbsp;Wen-Chu Zhao ,&nbsp;Hui-Sheng Chen","doi":"10.1016/j.neurot.2026.e00883","DOIUrl":"10.1016/j.neurot.2026.e00883","url":null,"abstract":"<div><div>We conducted a post hoc analysis of the ATAMIS (Antiplatelet Therapy in Acute Mild to Moderate Ischemic Stroke) trial to evaluate whether diabetes mellitus (DM) status affects the efficacy of antiplatelet therapy in acute mild-to-moderate ischemic stroke. Using the modified intention-to-treat analysis set from the ATAMIS trial, patients were categorized into DM and non-DM subgroups. Outcomes were compared between the two antiplatelet treatments in each subgroup, and an interaction between DM status and treatment efficacy was assessed. The primary efficacy endpoint was early neurological deterioration (END) at 7 days, and safety endpoints included bleeding events and intracranial hemorrhage. A total of 2915 patients were included in this study. Compared with aspirin monotherapy, clopidogrel plus aspirin significantly reduced the incidence of END at 7 days in patients with DM (5.2 % versus 8.8 %; adjusted risk difference, −4.1 %; 95 % CI, −8.1 % to −0.1 %; P = 0.04), but not in those without DM (4.6 % versus 6.1 %; adjusted risk difference, −1.9 %; 95 % CI, −4.0 %–0.2 %; P = 0.07). No significant interaction was observed between DM status and treatment effect on the primary outcome (P = 0.38). Safety endpoints were similar between treatment groups, regardless of DM status. In patients with acute mild-to-moderate ischemic stroke, dual antiplatelet therapy was associated with a significant reduction in END at 7 days, specifically in the DM subgroup.</div></div>","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 2","pages":"Article e00883"},"PeriodicalIF":6.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147453108","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}

{"title":"When gene replacement becomes a double-edged sword: Guardrails for precision neurotherapeutics in Lafora disease","authors":"Antonella Riva ,&nbsp;Pasquale Striano","doi":"10.1016/j.neurot.2026.e00885","DOIUrl":"10.1016/j.neurot.2026.e00885","url":null,"abstract":"","PeriodicalId":19159,"journal":{"name":"Neurotherapeutics","volume":"23 2","pages":"Article e00885"},"PeriodicalIF":6.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147458846","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}