Journal of Huntington's disease最新文献

Huntington's disease clinical trials update: August 2026. 亨廷顿氏病临床试验更新：2026年8月。

IF 2.7

Journal of Huntington's disease Pub Date : 2026-10-19 DOI: 10.1177/18796397261499360

Mena Farag, Opeyemi Kinyomi, Sarah J Tabrizi, Edward J Wild

{"title":"Huntington's disease clinical trials update: August 2026.","authors":"Mena Farag, Opeyemi Kinyomi, Sarah J Tabrizi, Edward J Wild","doi":"10.1177/18796397261499360","DOIUrl":"https://doi.org/10.1177/18796397261499360","url":null,"abstract":"In this edition, we highlight several important developments across the Huntington's disease therapeutic pipeline. We discuss the launch and subsequent discontinuation of POINT-HD, the first-in-human phase I study of RG6496 (Hoffmann-La Roche), an allele-selective antisense oligonucleotide designed to selectively lower mutant huntingtin while largely preserving wild-type huntingtin expression. We also discuss the launch of two phase III efficacy trials: INVEST-HD, evaluating votoplam (Novartis Pharmaceuticals), and PRECISE-HD, evaluating pridopidine (Prilenia). In addition, we summarise recent advances across the field, including preclinical updates for LQT-23 (LoQus23), SRP-1005 (Sarepta Therapeutics) and HRN001 (Harness Therapeutics); interim 12-month clinical results from SKY-0515 (Skyhawk Therapeutics); the announcement by uniQure that 3-year data from the phase I/II AMT-130 study may support a Biologics License Application seeking accelerated approval and Roche's discontinuation of the phase II GENERATION HD2 study of tominersen. Finally, we provide an updated listing of registered and ongoing clinical trials in Huntington's disease.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261499360"},"PeriodicalIF":2.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autonomic dysfunction in patients with Huntington's disease: Evidence from standardized cardiovascular reflex testing. 亨廷顿病患者的自主神经功能障碍：来自标准化心血管反射测试的证据

IF 2.7

Journal of Huntington's disease Pub Date : 2026-10-19 DOI: 10.1177/18796397261459542

Giannicola Carrozzo, Giovanna Calandra-Buonaura, Giulia Di Rauso, Maria Vitiello, Annagrazia Cerere, Giorgio Barletta, Pietro Cortelli, Pietro Guaraldi, Cesa Lorella Maria Scaglione

{"title":"Autonomic dysfunction in patients with Huntington's disease: Evidence from standardized cardiovascular reflex testing.","authors":"Giannicola Carrozzo, Giovanna Calandra-Buonaura, Giulia Di Rauso, Maria Vitiello, Annagrazia Cerere, Giorgio Barletta, Pietro Cortelli, Pietro Guaraldi, Cesa Lorella Maria Scaglione","doi":"10.1177/18796397261459542","DOIUrl":"https://doi.org/10.1177/18796397261459542","url":null,"abstract":"BackgroundAutonomic dysfunction has been reported in Huntington's disease (HD), but its extent and mechanisms remain unclear. This study aimed to evaluate autonomic function using standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of genetically confirmed HD patients.MethodsIn this single-center, cross-sectional study, we assessed 16 patients with manifest HD using head-up tilt test (HUTT), Valsalva maneuver (VM), deep breathing test, cold face test, and handgrip test, all performed under continuous blood pressure (BP) and heart rate (HR) monitoring. Age- and sex-matched healthy controls (HC) were included for comparison.ResultsBased on medical history, 56% of HD patients reported symptoms of orthostatic intolerance while standing. During HUTT, they showed a significant reduction in ΔBP. BP overshoot during VM was also significantly reduced. HR responses and BP changes did not differ significantly between groups across all other maneuvers. When stratified by disease stage, parasympathetic indices were lower in later-stage patients.ConclusionsHD patients exhibited subclinical adrenergic abnormalities on CRTs, with initially preserved cardiovagal control, a pattern compatible with central autonomic involvement and possible progressive impairment of both sympathetic and parasympathetic systems over time.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261459542"},"PeriodicalIF":2.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

iPSC neurodegenerative disease initiative isogenic CAG repeat iPSC line for Huntington's disease. 亨廷顿氏病的iPSC神经退行性疾病倡议等基因CAG重复iPSC系。

IF 2.7

Journal of Huntington's disease Pub Date : 2026-10-16 DOI: 10.1177/18796397261497434

Lisa Salazar, Mara S Burns, Jennifer T Stocksdale, Keona Q Wang, Gloria Cao, Ricardo Miramontes, Nicolette R McClure, Leanne Ho, Amber Rose Keith, Margaret Sutherland, Mark R Cookson, Michael Ward, William C Skarnes, Leslie M Thompson

{"title":"iPSC neurodegenerative disease initiative isogenic CAG repeat iPSC line for Huntington's disease.","authors":"Lisa Salazar, Mara S Burns, Jennifer T Stocksdale, Keona Q Wang, Gloria Cao, Ricardo Miramontes, Nicolette R McClure, Leanne Ho, Amber Rose Keith, Margaret Sutherland, Mark R Cookson, Michael Ward, William C Skarnes, Leslie M Thompson","doi":"10.1177/18796397261497434","DOIUrl":"https://doi.org/10.1177/18796397261497434","url":null,"abstract":"Purpose of ResearchThe generation of iPSC lines expressing 21, 56 and 79 glutamine repeats within the HTT protein and homozygous KO of HTT in the KOLF2.1J background as an additional disease series within the iPSC Neurodegenerative Disease Initiative (iNDI) collection.Major FindingsAll iPSCs, even those expressing long repeats of 79Q or HTT KO, were capable of differentiating to striatal and cortical neurons, astrocytes and microglia using established protocols. General quality control stains and morphological analyses are described for each differentiation. A selected set of assays were carried out on differentiated cells; expanded repeat expressing astrocytes showed altered expression of astrocyte protein markers and morphological characteristics, and striatal neurons showed altered DARPP-32/CTIP2 colocalization. mRNAseq carried out for striatal neurons showed high similarities in gene expression changes between 79Q and KO lines compared to the unexpanded repeat.ConclusionsThe KOLF2.1J isogenic CAG repeat series serves as a community resource to study HD mechanisms with the potential for direct comparison across other neurodegenerative diseases through the iNDI collection.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261497434"},"PeriodicalIF":2.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Directing mutant huntingtin towards degradation: Strategies and therapeutic opportunities. 引导突变的亨廷顿蛋白走向降解：策略和治疗机会。

IF 2.7

Journal of Huntington's disease Pub Date : 2026-10-09 DOI: 10.1177/18796397261494078

Florence Dm Wavreil, Sabine Schipper-Krom, Eric Aj Reits

{"title":"Directing mutant huntingtin towards degradation: Strategies and therapeutic opportunities.","authors":"Florence Dm Wavreil, Sabine Schipper-Krom, Eric Aj Reits","doi":"10.1177/18796397261494078","DOIUrl":"https://doi.org/10.1177/18796397261494078","url":null,"abstract":"Huntington's Disease (HD) is a progressive neurodegenerative disease that is caused by a CAG-repeat expansion in the exon 1 of the huntingtin (HTT) gene, which results in the formation of toxic mutant HTT (mHTT) exon 1 fragments with expanded polyglutamine (polyQ) stretch. These mHTT fragments are prone to misfolding and aggregation, causing cytotoxicity, particularly in the striatal neurons. The lack of disease-modifying treatments for HD emphasizes the need to develop new therapeutic strategies to prevent or reverse HD pathology. The reduction of the mHTT exon 1 fragment by facilitating its selective degradation may be a promising approach to prevent aggregation, thereby delaying or preventing the onset of HD. Since the ubiquitin-proteasome system (UPS) is not impaired in HD, enabling strategies to selectively target mHTT towards the UPS or autophagy would improve mHTT clearance. In this review, we describe three main strategies to modulate mHTT levels. First, we discuss different ubiquitin-modifying enzymes that have been associated with HTT and may act as possible therapeutic targets. Next, we focus on more targeted approaches for the selective degradation of mHTT with engineered small molecule compounds such as PROTACs and AUTOTACs. Finally, we summarize the current knowledge of HTT-specific intracellular antibodies (intrabodies) as potential candidates for gene therapy. Together, this review aims to assess different possible avenues for the treatment of HD.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261494078"},"PeriodicalIF":2.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defective membrane dynamics in Huntington's disease: A role of Rab11 dysfunction. 亨廷顿氏病的膜动力学缺陷：Rab11功能障碍的作用。

IF 2.7

Journal of Huntington's disease Pub Date : 2026-09-24 DOI: 10.1177/18796397261490952

An Wu, Xueyi Li

引用次数: 0

Esketamine for treatment of depression in Huntington's disease: A case report. 艾氯胺酮治疗亨廷顿病抑郁症1例报告

IF 2.7

Journal of Huntington's disease Pub Date : 2026-09-17 DOI: 10.1177/18796397261489245

Carsten Saft, Julia Jessen, David Kiefner, Georg Juckel

引用次数: 0

Chaperone-assisted selective autophagy (CASA) in polyglutamine-related diseases: From mechanisms to therapeutic perspectives. 伴侣辅助选择性自噬（CASA）在多谷氨酰胺相关疾病中的作用：从机制到治疗角度

IF 2.7

Journal of Huntington's disease Pub Date : 2026-09-03 DOI: 10.1177/18796397261478173

Barbara Tedesco, Marta Chierichetti, Riccardo Cristofani, Angelo Poletti

{"title":"Chaperone-assisted selective autophagy (CASA) in polyglutamine-related diseases: From mechanisms to therapeutic perspectives.","authors":"Barbara Tedesco, Marta Chierichetti, Riccardo Cristofani, Angelo Poletti","doi":"10.1177/18796397261478173","DOIUrl":"https://doi.org/10.1177/18796397261478173","url":null,"abstract":"Chaperone-assisted selective autophagy (CASA) is a crucial process aimed at maintaining proteostasis in several neurodegenerative diseases associated with protein misfolding, including polyglutamine (polyQ) diseases. Autophagy is a critical lysosome-mediated degradation pathway, particularly essential in neurons, which are highly susceptible to proteotoxic stress due to their post-mitotic nature. Selective autophagy pathways, including CASA, ensure the targeted removal of misfolded proteins and damaged organelles, thereby preserving cellular homeostasis. CASA is based on the intersection of chaperones and autophagy, where HSPB8 and BAG3 interact with HSPA and STUB1 forming a complex that identifies, ubiquitinates, and directs aberrant proteins toward autophagosomes for subsequent lysosomal degradation. In polyQ diseases, such as spinal and bul muscular atrophy (SBMA) and Huntington's disease (HD), mutant proteins accumulate, overwhelming the protein quality control systems. The CASA components are upregulated as a compensatory response, promoting toxic aggregates clearance and cellular damage mitigation. However, chronic proteotoxic stress and progressive impairment of autophagic and lysosomal pathways eventually limit CASA efficiency, contributing to disease progression. The review highlights how CASA exerts its protective activities in polyQ diseases and reports therapeutic strategies aimed at enhancing CASA activity, including pharmacological inducers and combinatorial approaches targeting autophagy and the ubiquitin-proteasome system. Overall, CASA emerges as a crucial adaptive mechanism and a promising therapeutic target in polyQ-related neurodegeneration.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261478173"},"PeriodicalIF":2.7,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Huntingtin, signaling endosomes and neuronal survival in health and Huntington disease. 亨廷顿蛋白，在健康和亨廷顿病中信号内体和神经元存活。

IF 2.7

Journal of Huntington's disease Pub Date : 2026-08-24 DOI: 10.1177/18796397261480227

Myriam Saliba, Frédéric Saudou, Chiara Scaramuzzino

{"title":"Huntingtin, signaling endosomes and neuronal survival in health and Huntington disease.","authors":"Myriam Saliba, Frédéric Saudou, Chiara Scaramuzzino","doi":"10.1177/18796397261480227","DOIUrl":"https://doi.org/10.1177/18796397261480227","url":null,"abstract":"The axonal transport of organelles mediates several functions throughout the lifespan of neurons. Over the past years, the role of endosomes, a specific type of trafficking organelle, has been extensively investigated for their increasing relevance during development, maturation and maintenance of neuronal networks. Endosome formation results from membrane invagination events driven by endocytic pathways. Following their formation, endosomes undergo maturation steps, and their fate is determined by the recruitment of specific cytosolic proteins to their membrane. Early endosomes may be recycled, signal in the distal compartments (signaling endosomes) or undergo fusion with autophagosomes (amphisomes), thus entering the degradation pathways together with lysosomes. Altogether, these processes regulate plasma membrane equilibrium at the synapse, further recycling and degradation of dysfunctional or toxic proteins, and promote the distribution of fundamental signals far from the synapses. Many of these pathways involve huntingtin (HTT) functions and are impaired in Huntington disease (HD). The past years have shed light on newly identified mechanisms involving the endocytic machinery with special attention being paid to long-range signaling endosome trafficking in axons. In this review, we will summarize the recent advancements and discuss the potential implications of therapeutic approaches to rescue these processes in the context of HD.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261480227"},"PeriodicalIF":2.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Indicators of need and timing of percutaneous endoscopic gastrostomy (PEG) in people with Huntington's disease: A medical chart review study. 亨廷顿舞蹈病患者需要经皮内镜胃造口术（PEG）的指标和时机：一项医学图表回顾研究

IF 2.7

Journal of Huntington's disease Pub Date : 2026-08-21 DOI: 10.1177/18796397261478175

Malin Sixt Börjesson, Mathias Hall, Elisabeth Winnberg

{"title":"Indicators of need and timing of percutaneous endoscopic gastrostomy (PEG) in people with Huntington's disease: A medical chart review study.","authors":"Malin Sixt Börjesson, Mathias Hall, Elisabeth Winnberg","doi":"10.1177/18796397261478175","DOIUrl":"https://doi.org/10.1177/18796397261478175","url":null,"abstract":"BackgroundIn the International guidelines for nutrition in Huntington's disease (HD) PEG-tubes may be considered in persons with HD (pwHD) with severe swallowing difficulties, but there are no general recommendations for when to initiate PEG-tube placement. Little is known about factors that have led to PEG-tube placements in pwHD.ObjectiveTo study the indications and timing of the PEG-tube placement in pwHD through medical chart review. Further aims were to investigate symptoms related to dysphagia, and documentation on informed consent to placement of the PEG-tube.MethodsRetrospective medical chart review on adult form of HD at two centers for HD in Sweden, from five years prior to the PEG-tube placement up to the closure of the data collection (minimum of 6 months post PEG).ResultsDysphagia-related chart notes were extracted from the medical charts of 14 pwHD. Indications for the PEG-tube placement were severe dysphagia (n = 11), weight loss (n = 10), preventive action initiated by the healthcare team (n = 5), own request by pwHD (n = 3) and recurrent aspiration pneumonia (n = 1). BMI was fluctuating both prior to and post PEG. Information about PEG-tube was documented 3 months to 4¼ years before PEG and documentation on informed consent was registered on 11 pwHD.ConclusionFrequency of dysphagia-related symptoms did not increase closer to PEG-tube placement and weight trends were inconclusive. Neither could be considered sufficient as an indicator of timing of PEG-tube placement. A request by the pwHD in combination with weight loss and/or severe dysphagia appeared to be a strong indicator for PEG-tube placement.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261478175"},"PeriodicalIF":2.7,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multimodal balance training with rhythmical auditory cueing in Huntington's disease: A pilot randomized controlled trial. 多模式平衡训练伴节奏听觉提示治疗亨廷顿舞蹈病：一项随机对照试验。

IF 2.7

Journal of Huntington's disease Pub Date : 2026-08-18 DOI: 10.1177/18796397261468393

Tamine Tc Capato, Jorik Nonnekes, Jordache Ramjith, Egberto R Barbosa, Joanna IntHout, Bastiaan R Bloem

{"title":"Multimodal balance training with rhythmical auditory cueing in Huntington's disease: A pilot randomized controlled trial.","authors":"Tamine Tc Capato, Jorik Nonnekes, Jordache Ramjith, Egberto R Barbosa, Joanna IntHout, Bastiaan R Bloem","doi":"10.1177/18796397261468393","DOIUrl":"https://doi.org/10.1177/18796397261468393","url":null,"abstract":"BackgroundBalance impairments in Huntington's Disease (HD) are common but difficult to treat.ObjectivesWe aimed to investigate the potential effects and feasibility of multimodal physiotherapy balance intervention in HD.MethodIn this prospective, double-blind, parallel group randomized clinical trial (phase 1pilot study), we screened 56 persons with genetically confirmed HD; 36 were assigned randomly into three groups: 1) multimodal physiotherapy balance intervention supported by rhythmical auditory stimuli (RAS-supported, n = 12); (2) multimodal physiotherapy balance intervention without rhythmical auditory stimuli (Regular, n = 12); and (3) control intervention (educational program, n = 12). Interventions were delivered for 2-months, at a low dose, 1 session/week. The primary outcome was the Mini-BESTest scored directly after the intervention. All outcomes were assessed at three time-points.ResultsDirectly post-intervention, both the RAS-supported group and the Regular group improved significantly on the Mini-BESTest score compared to the Control group (RAS-supported 4.2 (95% Confidence Interval(CI) 3.1; 5.2), p < 0.001; Regular 2.7 (CI 1.7; 3.6), p < 0.001. These improvements were retained at 6-month follow-up only for the RAS-supported group.ConclusionThese findings motivate future studies to further explore multimodal physiotherapy interventions to improve balance in HD.","PeriodicalId":16042,"journal":{"name":"Journal of Huntington's disease","volume":" ","pages":"18796397261468393"},"PeriodicalIF":2.7,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0