Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

{"title":"Interleukin-6 in ALS: metabolic mediator or marker of ventilatory decline?","authors":"Ana Catarina Pronto-Laborinho, Mamede De Carvalho","doi":"10.1080/21678421.2026.2667283","DOIUrl":"https://doi.org/10.1080/21678421.2026.2667283","url":null,"abstract":"","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-2"},"PeriodicalIF":2.8,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147846762","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}

{"title":"Pridopidine treatment in ALS: subgroup analyses from the HEALEY ALS Platform trial.","authors":"Michal Geva, Y Paul Goldberg, Melanie L Leitner, Andres Cruz-Herranz, Randal Hand, Kelly Chen, Noga Gershoni Emek, Andrew M Tan, Sabrina Paganoni, James D Berry, Eric A Macklin, Jeremy M Shefner, Merit E Cudkowicz, Michael R Hayden","doi":"10.1080/21678421.2025.2597935","DOIUrl":"10.1080/21678421.2025.2597935","url":null,"abstract":"<p><p><i>Objectives</i>: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options. Pridopidine, a selective sigma-1 receptor agonist, was evaluated in Regimen D of the HEALEY ALS Platform Trial. Although the primary endpoint (ALS Functional Rating Scale-Revised (ALSFRS-R) total score accounting for survival at 24 weeks) was not met, a predefined subgroup analysis suggested slowed disease progression in ALS patients with definite and early disease (<18 months from onset). This report presents an exploratory analysis that further investigates pridopidine in rapidly progressing participants with definite/probable ALS and early-disease, where treatment effects may be more pronounced. <i>Methods</i>: The randomized, double-blind, placebo-controlled phase 2 trial assigned participants to pridopidine 45 mg bid or placebo, and placebo patients were shared across four trial regimens. The primary outcome was ALSFRS-R total score, with secondary outcomes assessing respiratory, bulbar, and speech functions. <i>Results</i>: Of 163 participants randomized to Regimen D, 72 met subgroup criteria (pridopidine: <i>n</i> = 37; shared placebo: <i>n</i> = 35). At week 24, pridopidine slowed ALSFRS-R total score decline (32%; Δ2.90, <i>p</i> = 0.03) and slowed decline of ALSFRS-R respiratory function (62%; Δ1.20, <i>p</i> = 0.03) and dyspnea (88%; Δ0.85, <i>p</i> = 0.005). ALSFRS-R-Bulbar function stabilized, with articulation and speaking rate declines reduced by 93% (Δ0.43, <i>p</i> = 0.0007) and 70% (Δ0.43, <i>p</i> = 0.002), respectively. Pridopidine was well-tolerated, with a safety profile comparable to placebo. All <i>p</i> values are nominal. <i>Conclusion: Post hoc</i> subgroup analysis suggests therapeutic benefits of pridopidine in patients that had definite/probable ALS and with early-disease progression, supporting further evaluation in a Phase 3 trial.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"432-444"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776054","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}

{"title":"How effective does a new drug for Amyotrophic Lateral Sclerosis need to be - the patient perspective: a letter in response to \"Estimating the minimum important difference in the ALSFRS-R-instrument in people living with MND\" published in vol. 26, pp. 249-258.","authors":"Andrew Darke, Cali Orsulak","doi":"10.1080/21678421.2025.2589781","DOIUrl":"https://doi.org/10.1080/21678421.2025.2589781","url":null,"abstract":"","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":"27 3-4","pages":"485-486"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790490","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}

{"title":"Quality of life and care burden of people living with amyotrophic lateral sclerosis who need home-based medical care in Korea and their family caregivers.","authors":"Shin Hye Yoo, Belong Cho, Kyae Hyung Kim, In Young Hwang, Woohyeon Cho, Seok-Jin Choi, Jung-Joon Sung, Sun Young Lee","doi":"10.1080/21678421.2025.2589780","DOIUrl":"10.1080/21678421.2025.2589780","url":null,"abstract":"<p><p><i>Objective</i>: Advanced neurodegenerative diseases (NDDs) lead to severe mobility limitations, creating significant challenges for patients and caregivers at home. We aimed to investigate the quality of life (QOL) and care burden of people living with amyotrophic lateral sclerosis (ALS, pALS) and other NDDs and their family caregivers in Korea. <i>Methods</i>: This prospective survey study included people living with NDDs with mobility restrictions and their caregiver enrolled in a home-based medical care (HBMC) program at one tertiary hospital in South Korea from 2022 to 2024. Data collected included demographics, clinical characteristics, care burden (the Zarit Caregiver Burden Interview Short Form, ZBI-12), QOL (EQ-5D-5L), and depression (Patient Health Questionnaire-9). The results were compared between ALS and other NDDs (non-ALS). <i>Results</i><b>:</b> Of 44 patients requiring HBMC, 70.5% (31) were pALS. pALS were younger than non-ALS (median age, 65 vs. 79 years); more often, the caregiver was a spouse (64.5% vs. 46.1%, <i>p</i> = 0.30). One-fourth (25.8%) of pALS were on polypharmacy (>10 medications a day). One-third (29%) of pALS and 22.6% of their caregivers experienced moderate or severe depression. Half of pALS caregivers experienced high caregiving burden (ZBI-12 score ≥17). The mean EQ-5D-5L index score was 0.48 for pALS and 0.84 for their caregivers, which was lower than the results for the Korean general population. <i>Conclusions:</i> Patients with severe NDD and caregivers experienced low QOL and high caregiving burden, with pALS caregivers particularly vulnerable to depression and heavy burden. Designing optimal HBMC programs to support pALS and home caregivers is warranted.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"274-284"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552115","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}

{"title":"A study of patient recall and comprehension of genetic testing results in amyotrophic lateral sclerosis (ALS).","authors":"Jewel Tomlinson, Emily Roberson, Victoria Klee, Jianing Ma, Jennifer Roggenbuck","doi":"10.1080/21678421.2025.2582829","DOIUrl":"10.1080/21678421.2025.2582829","url":null,"abstract":"<p><p><i>Objective:</i> Assess the accuracy of ALS patient recall of genetic testing results and evaluate comprehension of key implications of results. <i>Methods:</i> Participants were recruited from the Center for Disease Control's National ALS Registry. A survey collected participant demographics, their recollection of their genetic test result, and their understanding of the implications of their result. Comprehension was scored based on responses to key questions. Whenever possible, patient-reported test results were confirmed by review of their test report. <i>Results:</i> Most participants (n = 246) were white (n = 238, 96.7%) with high health literacy. Among participants whose self-reported result could be validated, most 93/98 (94.9%) accurately recalled whether they received a positive, negative, or uncertain result. Among participants who reported positive results, 32/50 (64.0%) demonstrated understanding that their genetic testing results explained their ALS, while 38/50 (76.0%) accurately characterized the risk that first degree relatives carried the same variant. Among participants who reported negative results, 100/142 (70.4%) incorrectly indicated that their result ruled out a genetic cause. When asked about the risk for family members to develop ALS, 98/142 (69.0%) correctly characterized this residual risk. However, only 12/142 (8.5%), answered both questions correctly. Overall, participants who saw a genetic counselor were more likely to demonstrate high comprehension (p = 0.022). <i>Conclusions:</i> The majority of participants demonstrated accurate recall of their ALS genetic testing result. However, deficits in understanding of key implications were identified, particularly among those with negative results. Participants who saw a genetic counselor had significantly better comprehension of their test results than those who did not.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"363-369"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460550","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}

{"title":"Incidence of MND in Canterbury, New Zealand and impact of a key worker role on hospital admissions.","authors":"Rachel Wiseman, Justin Jordan, Malina Storer, Michael Epton","doi":"10.1080/21678421.2025.2604231","DOIUrl":"10.1080/21678421.2025.2604231","url":null,"abstract":"<p><p><i>Objective</i>: To establish the incidence of MND in Canterbury, New Zealand between 2008 and 2020, building on previously published local data. To investigate any change in hospital and emergency department use, timing of feeding tube insertion or initiation of noninvasive ventilation (NIV) after introduction of a Key Worker role and multidisciplinary clinic. <i>Methods</i>: A retrospective audit of medical records from patients diagnosed with MND between 2008-2012 and 2015-2019, before and after creation of a Key Worker role in 2013. Three separate local databases were searched to identify all cases. Medical records were searched to identify patients who met the inclusion criteria and capture hospital admissions/emergency department visits, date of feeding tube insertion and/or initiation of NIV for each patient. <i>Results</i>: Incidence averaged 3.36 diagnoses per 100,000 population per year and remained relatively stable between 2008 and 2020. There was no difference between the two time cohorts in the likelihood or timing of feeding tube insertion or initiation of NIV. There was a significant reduction in unplanned hospital admissions and emergency department visits in the latter time period, after initiation of the key worker role and multidisciplinary clinic. <i>Conclusions</i>: Incidence of MND in Canterbury, New Zealand remains relatively stable. Implementation of a Key Worker role may be related to reduced hospital admissions and emergency department visits.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"404-411"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812312","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}

{"title":"Homozygosity for the C allele at <i>UNC13A</i> rs12608932 seems to compromise cognition in ALS independently of the cognitive domains.","authors":"Annaliis Lehto, Andreas Zapf, Andreas Hermann, Judith Machts, Stefan Vielhaber, Jonas Koppenbrink, Dieter Edbauer, Elisabeth Kasper, Johannes Prudlo","doi":"10.1080/21678421.2025.2608238","DOIUrl":"10.1080/21678421.2025.2608238","url":null,"abstract":"<p><p>The common single nucleotide polymorphism (SNP) rs12608932 located at a cryptic splice in the <i>UNC13A</i> gene has been reported to modify the clinical phenotype of ALS, but it is unclear whether homozygosity for the C-allele at <i>UNC13A</i> rs12608932 modifies specific domains of cognition in ALS. We analyzed retrospective data from a German cohort and found that the proportion of cognitively or behaviorally impaired patients was higher in the high-risk group of homozygous C-allele carriers. Patients with C/C alleles had lower scores than controls on verbal fluency, executive functioning, and delayed memory recall, but did not differ significantly from other ALS genotypes. Furthermore, informant ratings suggested higher disinhibition in the C/C carriers. These findings indicate that the C/C risk variant of <i>UNC13A</i> rs12608932 may contribute to general cognitive vulnerability rather than domain-specific deficit.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"348-351"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893506","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}

{"title":"The impact of motor neurone disease on oral health: a scoping review.","authors":"Jessica Hewitt-Dean, Jessie Tebbutt, Esther Hobson","doi":"10.1080/21678421.2025.2603312","DOIUrl":"10.1080/21678421.2025.2603312","url":null,"abstract":"<p><strong>Objective: </strong>To identify current evidence on oral health-related quality of life in people with Motor Neurone Disease (MND), as well as identify barriers to oral health and care, and establish priorities for future research.</p><p><strong>Methods: </strong>A scoping review was conducted. Electronic databases and grey literature sources were searched from 2000 to 2024. Articles discussing oral health in adults with MND were included. Findings were supplemented by stakeholder consultation with people with MND, caregivers, clinicians, and researchers.</p><p><strong>Results: </strong>Fourteen articles met inclusion criteria, comprising eight cross-sectional studies, one prospective quality improvement project, one single center observational and four review articles. Five key themes emerged: dental status and oral hygiene activities, orofacial function, secretion management, service delivery and Oral health-related quality of life (OHRQoL). Studies indicated that MND negatively impacts oral health through impaired ability to perform oral hygiene and altered orofacial functioning. Only one study examined oral health-related quality of life. Stakeholder consultation highlighted additional concerns including challenges with service access, the impact of MND on oral health, and difficulties maintaining oral hygiene due to physical limitations.</p><p><strong>Conclusions: </strong>Oral health remains an under-researched area in MND care despite its potential impact on quality of life and overall wellbeing. Future research priorities should include investigating relationships between oral health and MND outcomes, improving service delivery models, and increasing dental professional awareness. Active involvement of people with MND in research design and implementation is essential for developing effective interventions.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"239-245"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913979","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}

{"title":"Minimum important slowing of disease progression as determined by the ALS functional rating scale - a survey of patient expectations toward disease-modifying drugs in ALS.","authors":"Thomas Meyer, André Maier, Torsten Grehl, Ute Weyen, Annekathrin Rödiger, Uta Smesny, Robert Steinbach, Julian Grosskreutz, Bettina Göricke, Sarah Bernsen, Patrick Weydt, Rachel Fabian, Susanne Petri, Rea Lumi, Bogdan Bjelica, Matthias Boentert, Paul Lingor, Dagmar Kettemann, Jenny Norden, Bertram Walter, Alessio Riitano, Peggy Schumann, Christoph Münch, Susanne Spittel","doi":"10.1080/21678421.2026.2615117","DOIUrl":"10.1080/21678421.2026.2615117","url":null,"abstract":"<p><p><i>Objective:</i> To define the minimum important slowing (MIS) of ALS progression that patients would expect from disease-modifying drug treatment in ALS. <i>Methods:</i> In a survey of ALS patients, the MIS in ALS progression (change in the ALS Functional Rating Scale-Revised, ALSFRS-R) was assessed by asking: \"At what point of slowing of ALS, as determined by the ALSFRS-R, do you consider a drug to be important?\" Data were collected during clinic visits or remotely via the ALS App. Participants were differentiated in the prognostic groups of slower (<0.5), intermediate (≥0.5 and ≤1.0), or faster (>1.0) ALS progression (ALSPR; ALSFRS-R/month). <i>Results:</i> Of 522 participants (ALS App, <i>n</i> = 397; clinic, <i>n</i> = 125), 395 (75.7%) completed the survey, while 127 (24.3%) selected the option \"cannot estimate\". The distribution of MIS was as follows: modest slowing of ALS progression (5% and 10% slowing, <i>n</i> = 146 patients, 36.9%), moderate slowing (20%, 30%, and 40% slowing, <i>n</i> = 135, 34.2%), and major slowing (≥50% slowing, <i>n</i> = 114, 28.9%). Median MIS was 20% (IQR 10-50%). Patients with faster ALSPR more frequently assessed a major slowing as the MIS (<i>n</i> = 18, 36.0%) compared to those with slower ALSPR (<i>n</i> = 54, 25.2%). <i>Conclusion:</i> A considerable number of participants viewed a modest slowing in ALS progression as the MIS, followed closely by preferences for moderate and major slowing. Expectations varied according to patients' individual ALS progression. These insights may inform the design of future clinical trials in ALS. Study limitations include potential selection and response biases, as well as the predominantly remote digital assessment.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"457-468"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013596","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}

{"title":"Examining IGFBP7 as a potential therapeutic target in people with ALS.","authors":"Andrew Brown, Colin Stubberfield, Fernando Vieira, Richard Bedlack","doi":"10.1080/21678421.2025.2559441","DOIUrl":"10.1080/21678421.2025.2559441","url":null,"abstract":"<p><p>A single nucleotide variant in an insulin-like growth factor (IGFBP7) promotor, which reduces IGFBP7 levels in brain, was previously associated with an ALS \"reversal\" phenotype. This raises the question of whether IGFBP7 might be a therapeutic target in ALS. Here, we use a combinatorial analysis to show that IGFBP7-Antisense (AS1) is associated with resistance to ALS. In ALS patients' blood, we demonstrate increased IGFPB7 protein relative to healthy controls. In ALS patients' spinal cords and iPS-derived motor neurons, we demonstrate increased IGFBP7 mRNA levels relative to healthy controls. These four new analyses support IGFBP7 as a possible therapeutic target in ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"477-480"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145055387","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}