Amyotrophic lateral sclerosis & frontotemporal degeneration最新文献

{"title":"Types and frequencies of adverse events across clinical trials for patients with amyotrophic lateral sclerosis: an analysis of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.","authors":"Sangmi Kim, Sarah E Curtis, Diego Iacono, Nicole F Mehdiyoun, Lucy Mitchell, Angela Genge, Alexander U Brandt, Michele Mancini","doi":"10.1080/21678421.2026.2667290","DOIUrl":"10.1080/21678421.2026.2667290","url":null,"abstract":"<p><strong>Objective: </strong>Symptoms of amyotrophic lateral sclerosis (ALS) may present as adverse events (AEs) in ALS clinical trials. Identifying anticipated AEs independent of investigational drug is crucial for trial design and required by the FDA for safety reporting and assessment in drug development. This study describes anticipated AEs and their predicted incidence in ALS trials, leveraging data from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.</p><p><strong>Methods: </strong>Placebo-treated people living with ALS (age ≥18 years, disease duration ≤36 months, ≥50% of predicted vital capacity at screening) were included. A confirmed diagnosis per the El Escorial criteria was required for a sensitivity analysis. Reported AEs were grouped based on pathophysiology and implications in clinical management and safety monitoring. AEs were further consolidated, with seven anticipated groups pre-specified for analysis. AE incidence proportions (IPs) and rates in person-years were estimated.</p><p><strong>Results: </strong>The analysis included 1,388 participants (mean [SD] age: 56.8 [11.3] years; mean [SD] disease duration: 1.4 [0.6] years). IP was ≥5% for 24 AE groups, highest for falls and injuries (18.8%), headaches (13.5%), muscle weakness (13.1%), and gastrointestinal signs and symptoms (13.1%). Of seven pre-specified AE groups, falls, injuries, and fractures were the most frequent (23.0%), followed by severe respiratory failure and disorders including dyspnea (19.1%) and dysphagia (10.5%). Sensitivity analysis results were comparable (n = 931), although IPs were generally lower.</p><p><strong>Conclusions: </strong>These new findings will facilitate a systematic approach for safety monitoring and reporting in ALS trials, enable detection of true safety signals that may be obscured by these events, and support clinical development.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"920-930"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984481","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":"From theory to practice: physicians' knowledge, attitudes, and practices regarding amyotrophic lateral sclerosis in Egypt - a cross-sectional study.","authors":"Ahmed Dahshan, Marwa I M Khalil, Heba A D A Deraz","doi":"10.1080/21678421.2026.2652326","DOIUrl":"10.1080/21678421.2026.2652326","url":null,"abstract":"<p><strong>Background: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with heterogeneous presentations that often mimic other conditions, leading to frequent misdiagnosis and delayed recognition. Physician awareness and diagnostic confidence are critical for early detection, yet little is known about these factors in the Middle East and North Africa (MENA) region, where ALS services and specialized centers remain limited.</p><p><strong>Methods: </strong>We conducted a nationwide cross-sectional survey of 1,320 physicians in Egypt. A validated online questionnaire assessed demographics, knowledge, attitudes, and practice patterns regarding ALS. Data were analyzed using appropriate statistics, with multivariate regression to identify predictors of knowledge, attitudes, and practices.</p><p><strong>Results: </strong>Overall, 41.0% of physicians demonstrated poor knowledge of ALS, while only 8.8% achieved good knowledge. Nearly half (46.5%) reported little or no diagnostic confidence, and 93.7% expressed a strong need for additional educational programs. Most respondents identified MRI (78.3%) as the main diagnostic test, whereas only 2.0% selected electrophysiological studies. Nevertheless, practice scores were higher: 65.7% reported good practice levels and 48.4% indicated they would directly refer suspected cases to specialists. Knowledge strongly correlated with attitudes (<i>r</i> = 0.610, <i>p</i> < 0.001) and both were moderately correlated with practice. Multivariate analysis identified neurology specialty, postgraduate ALS training, and urban practice as independent predictors of better knowledge and attitudes, while greater experience predicted improved practice.</p><p><strong>Conclusion: </strong>Egyptian physicians show limited ALS knowledge and low diagnostic confidence despite reasonable practice behaviors. Training and structured referral pathways are urgently needed to improve ALS preparedness in Egypt and the wider MENA region.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"777-784"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610816","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":"Challenges in medical care for amyotrophic lateral sclerosis: a survey of physicians from Republic of Bashkortostan (Russia), Belarus, and Kazakhstan.","authors":"Ekaterina V Pervushina, Yuliya N Rushkevich, Saule T Turuspekova, Mansur A Kutlubaev","doi":"10.1080/21678421.2026.2652327","DOIUrl":"10.1080/21678421.2026.2652327","url":null,"abstract":"<p><strong>Objective: </strong>To identify and compare the main challenges in diagnosing and managing amyotrophic lateral sclerosis (ALS) from the perspective of neurologists in Republic of Bashkortostan (Russia), Belarus, and Kazakhstan.</p><p><strong>Methods: </strong>An anonymous online survey was distributed to neurologists via professional networks from May to October 2025. The questionnaire collected data on demographics, diagnostic and therapeutic approaches, barriers, and suggestions for improvement.</p><p><strong>Results: </strong>The survey included 294 neurologists. Over half (58.2%) diagnosed ALS less than once a year. Major diagnostic barriers were limited access to key investigations like electromyography (62.6%) and a lack of specialized ALS centers (37.8%). For treatment, 48% prescribed riluzole, while only 12.9% used edaravone. Critically low rates of gastrostomy placement and respiratory support provision (<10% of terminal patients) were noted by over 80% of respondents. Significant cross-country differences were found: neurologists in Kazakhstan utilized genetic testing and edaravone more frequently; neurologists in Belarus employed muscle/tongue ultrasound more often; neurologists in the Republic of Bashkortostan (Russia) reported higher use of speech therapy and gastrostomy. The most frequently proposed solutions were establishing specialized ALS centers (34%), enhancing physician training (20%), and improving palliative care services (16.5%).</p><p><strong>Conclusions: </strong>This multinational survey provides important insights into ALS care in the studied countries, identifying key areas for further development. The results point to opportunities for enhancing diagnostic resources, therapeutic strategies, and palliative care approaches. Enhancing the quality of ALS care requires the development of specialized clinical pathways, the implementation of consensus-based protocols, and the expansion of professional education in multidisciplinary management.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"785-792"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694095","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":"Diagnostic differences between military veterans and non-veterans: data from the United States National ALS Registry.","authors":"Jaime Raymond, Theodore Larson, Suraya Mohidul, Drake Martin-Greene, Kirt Love, Vincent Mehta, James Wymer, Ileana Howard, D Kevin Horton, Paul Mehta","doi":"10.1080/21678421.2026.2677528","DOIUrl":"10.1080/21678421.2026.2677528","url":null,"abstract":"<p><p><i>Background and Aim:</i> Veterans in the U.S. have been reported to have a higher risk of developing amyotrophic lateral sclerosis (ALS) than the general population. However, it is unclear whether veterans experience differences in symptom recognition, diagnostic timing or access to care. This study examined differences reported in clinical characteristics and diagnostic trajectories between male veteran (MV) and non-veteran male (NVM) ALS patients enrolled in the U.S. National ALS Registry. <i>Methods:</i> We conducted a propensity score-matched analysis using self-administered military and clinical surveys from 2014 to 2024. Among 2,891 male ALS patients, MV were matched 1:1 with NVM on smoking history, birth year, head injury history, and region of residence at diagnosis. Outcomes included reported symptoms, time from symptom onset to diagnosis, and time to selected interventions. <i>Results:</i> Overall, 802 MV were matched to 802 NVM. Veterans were older at and reported longer intervals from symptom onset to ALS diagnosis (20.8 vs 16.7 months, <i>p</i> = 0.0004). MV were more likely to report difficulty swallowing and falls. Veterans were also more likely to use noninvasive breathing equipment (<i>p</i> = 0.0322). Findings from time-to-event analyses showed MV received wheelchairs or scooters statically earlier than NMV (log-rank <i>p</i> = 0.0028). <i>Conclusions:</i> Among participants in the Registry, MV reported differences in diagnostic timing, symptoms, and the use of supportive interventions compared to NVM. These findings may reflect differences in healthcare access, care pathways, and disease recognition over intrinsic differences in ALS biology. Because Registry participation is voluntary and data are self-reported, the result may not be generalizable to the broader ALS population.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"837-846"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058443","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":"Understanding psychological adjustment in patients with amyotrophic lateral sclerosis and their caregivers: a scoping review.","authors":"Marion Sommers-Spijkerman, Fabiola Müller, Esther Kruitwagen-Van Reenen, Johanna M A Visser-Meily, Rien Uitslag, Anita Beelen","doi":"10.1080/21678421.2026.2671166","DOIUrl":"10.1080/21678421.2026.2671166","url":null,"abstract":"<p><strong>Objective: </strong>Psychological adjustment is a major focus in the care of people with amyotrophic lateral sclerosis (ALS) and their caregivers, given its critical role in maintaining quality of life (QoL). This scoping review aimed to gain a better understanding of ALS patients' and caregivers' psychological adjustment, to inform future care and research.</p><p><strong>Methods: </strong>PubMed, Web of Science, PsycINFO, Embase and CINAHL were searched for peer-reviewed studies reporting associations of psychological factors with patient/caregiver QoL. Psychological factors were categorized by type (cognitive, emotional or behavioral responses), and by strength (weak, moderate, strong) and direction (positive, negative) of their association with patient/caregiver QoL.</p><p><strong>Results: </strong>Twenty-nine studies were included, identifying twelve cognitive responses (hope, positive thinking/reframing, psychological flexibility, resilience, coping/pain self-efficacy, helplessness, hopelessness, pain catastrophizing, rumination, self-perceived burden, self-stigma), two emotional responses (emotional support, venting) and three behavioral responses (independence, positive action, substance use) associated with patient QoL. Five cognitive responses (resilience, mindfulness, hopelessness, passive reaction coping, psychological inflexibility) and one behavioral response (positive action) were found associated with caregiver QoL.</p><p><strong>Conclusions: </strong>A range of cognitive, emotional and behavioral responses, most notably cognitive responses, were found to shape patient and/or caregiver psychological adjustment, hence may serve as potential targets in ALS clinical practice. Nonetheless, empirical evidence is limited by heterogeneity in outcomes and measures and a lack of longitudinal, multivariable, and caregiver-oriented research. More systematic, standardized and longitudinal data collection is needed to clarify how psychological adjustment processes evolve throughout the disease trajectory and to identify modifiable targets for psychological supportive care.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"896-909"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058486","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":"Oligogenic variants in <i>NEK1</i> and <i>ATXN2</i> in amyotrophic lateral sclerosis: report of two cases and review of the literature.","authors":"Émy Roy, Mathieu Blais, Patrick Dion, Guy A Rouleau, Nicolas Dupré, Vincent Picher-Martel","doi":"10.1080/21678421.2026.2685158","DOIUrl":"10.1080/21678421.2026.2685158","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects the upper and lower motor neurons and leads to progressive paralysis. More than 40 genes have been implicated in familial ALS, which represents about 10% of ALS cases. Some genes, including <i>C9orf72</i>, <i>SOD1</i>, <i>FUS</i> and <i>TARDBP</i> are undoubtedly considered causative, but many others have uncertain pathogenicity and low penetrance. Here, we described the cases of two siblings affected by ALS and carrying both an <i>ATXN2</i> heterozygous 32 CAG trinucleotide repeat expansion and a novel <i>NEK1</i> heterozygous c.1674_1677dup. The segregation of both variants in this large family with thirteen siblings may support a role for these variants as susceptibility alleles within an oligogenic model. Our review of the literature suggests that <i>NEK1</i> variants are frequently found in combination with other variants and repeats expansion in the <i>ATXN2</i> gene appears to be more associated with monogenic ALS, but also frequently combined with <i>C9orf72</i> repeat expansion.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"856-864"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221085","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":"Primary lateral sclerosis in Brazil: phenotypic heterogeneity, non-motor features, and prognostic markers in a 17-year multicentre cohort.","authors":"Christian Marques Couto, Cecilia Vidal Watkins, Ricardo Silva Carvalho, Eduardo Boiteux Uchoa Cavalcanti, Alessandra De La Roque Ferreira, Waneska Souza Lima, Osvaldo José Moreira Nascimento","doi":"10.1080/21678421.2026.2652325","DOIUrl":"10.1080/21678421.2026.2652325","url":null,"abstract":"<p><p><i>Objective:</i> Primary lateral sclerosis (PLS) is a rare upper motor neuron disorder within the motor neuron disease spectrum. Data from Latin America remains limited. We aimed to characterize clinical phenotypes, non-motor features, and prognostic markers in a systematically adjudicated Brazilian PLS cohort. <i>Methods:</i> In this retrospective multicenter study, we analyzed the data of 81 patients meeting the Turner 2020 criteria for probable/definite PLS at SARAH Network Hospitals (2007-2023). Clinical phenotyping, neurophysiology, <i>C9orf72</i> testing, and survival analyses were conducted. <i>Results:</i> The participants' median age at onset was 54 years (interquartile range 46-62); 53% of them were men. The onset distribution was as follows: lower limb 65%, bulbar 22%, and upper limb 11%. Extrapyramidal signs (7%) identified high-risk patients with fourfold increased mortality (relative risk [RR] 4.2, <i>p</i> = 0.013) and sixfold increased cognitive impairment (RR 6.3, <i>p</i> = 0.007). Eight patients (9.9%) exhibited hemiparetic presentations, with two meeting the definite Mills syndrome criteria; seven patients progressed to generalized PLS. Non-motor features were common: pseudobulbar affect (51%), urinary urgency (57%), and cognitive impairment (11%). Family history was observed in 10% and <i>C9orf72</i> expansion in 3%, with intrafamilial phenotypic variability. Five-year survival was excellent (98%) without onset-site effect (hazard ratio 0.80, <i>p</i> = 0.697). Two patients maintained isolated corticobulbar syndrome for 50-71 months. <i>Conclusions:</i> This first Latin American PLS cohort demonstrates clinical characteristics comparable to those reported in international studies. Extrapyramidal signs emerged as a high-risk marker. Hemiparetic presentations appear transitional, and non-motor manifestations support PLS as a multisystem disorder.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"767-776"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679193","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":"Fast and controlled access to tofersen for <i>SOD1</i>-related amyotrophic lateral sclerosis in The Netherlands; experiences using the orphan drug access protocol.","authors":"Sean W Willemse, Carla E M Hollak, Niels D Reijnhout, Carelle C Reparon-Schuijt, Anke A M G Pisters-van Roy, Koen C Demaegd, Ruben P A van Eijk, Leonard H van Den Berg, Michael A van Es","doi":"10.1080/21678421.2026.2655738","DOIUrl":"10.1080/21678421.2026.2655738","url":null,"abstract":"","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"946-948"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679221","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":"Molecular and genetic landscape of amyotrophic lateral sclerosis in Latin America: a scoping review of pathogenic hypotheses and ancestral heterogeneity.","authors":"Sergio V Flores, Patricia Lillo, Jorge Briceño-Moya, Ailin Pino-San Pedro","doi":"10.1080/21678421.2026.2668070","DOIUrl":"10.1080/21678421.2026.2668070","url":null,"abstract":"<p><p><i>Background</i>: The genetic architecture of amyotrophic lateral sclerosis (ALS) has been predominantly characterized in populations of European ancestry, while Latin American populations remain underrepresented despite their complex admixture. <i>Objective</i>: To map the molecular hypotheses explored in ALS research conducted in Latin American populations and identify key methodological and structural gaps. <i>Methods</i>: A scoping review was conducted following Joanna Briggs Institute methodology and reported according to PRISMA-ScR guidelines. Searches were performed in Web of Science, Scopus, PubMed/MEDLINE, SciELO, and LILACS. Studies investigating genetic or molecular aspects of ALS or the ALS-FTD spectrum in Latin American populations were included. Data were extracted using a standardized matrix and synthesized descriptively. <i>Results</i>: Nineteen studies met inclusion criteria. Most were small, single-center investigations employing targeted candidate-gene approaches, predominantly focused on C9orf72 expansions and SOD1 mutations. Reported C9orf72 frequencies varied substantially across countries, indicating population-specific genetic heterogeneity. Only one study incorporated explicit ancestry inference, and no genome-wide association studies or large multicenter ALS genomic cohorts were identified. <i>Conclusions</i>: ALS research in Latin America remains limited, fragmented, and largely candidate-gene driven, with minimal integration of ancestry-informed approaches. The absence of large-scale genomic studies, despite existing regional sequencing capacity, highlights the need for coordinated multicenter initiatives to enable equitable implementation of precision medicine.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"739-747"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864809","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":"ALS untangled #83: clenbuterol.","authors":"Adam Burgess, Olivia Allen, Paul Barkhaus, Benjamin Barnes, Michael Benatar, Tulio Bertorini, Robert Bowser, Javier Mascias Cadavid, Gregory T Carter, Merit Cudkowicz, Keelie Denson, Kara Dyckman, Basil Elsharif, Eva Feldman, Juliette Foucher, Timothy Fullum, Jonathan Glass, Benjamin Helmold, Carlayne Jackson, Sartaj Jhooty, Ariah Leday, Elise Mallon, Christopher Mcdermott, Natasha Olby, Lyle Ostrow, Gary Pattee, Erik Pioro, Dylan Ratner, Hemangi Sang, Elia Tito, Fernando Vieira, Paul Wicks, Richard Bedlack, Dario Gelevski","doi":"10.1080/21678421.2026.2638588","DOIUrl":"10.1080/21678421.2026.2638588","url":null,"abstract":"<p><p>ALS Untangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review clenbuterol, a β-2 adrenergic agonist, as a potential treatment for amyotrophic lateral sclerosis (ALS). Clenbuterol has biological effects that could be relevant to the pathophysiology of ALS such as inducing muscle hypertrophy, improving mitochondrial function, and reducing neuroinflammation. Two studies in mouse models of motor neuron disease and two open label trials suggest possible benefits. However these have methodological flaws which limit interpretation. Clenbuterol can have an array of side effects, some severe. Drop-outs due to side effects were very common in one of the ALS trials and in a separate expanded access program. Based on this information, we cannot currently endorse clenbuterol as an ALS treatment, but we do hope to see further studies of it, or another long acting β-2 adrenergic agonist in people with ALS.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"949-956"},"PeriodicalIF":2.8,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379783","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}