Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration最新文献

{"title":"Platform Communications: Abstract Book – 33rd International Symposium on ALS/MND (Complete printable file)","authors":"S. Appel, J. Thonhoff, J. Berry, D. Beers, E. Macklin, M. Cudkowicz","doi":"10.1080/21678421.2022.2082738","DOIUrl":"https://doi.org/10.1080/21678421.2022.2082738","url":null,"abstract":"Neuroinflammation plays a prominent role in promoting the disease progression of ALS, mediated in part by the interaction of injured motoneurons with surrounding glia and dysregulated central and peripheral immunomodulatory cells. Prominent among such immunomodulatory cells are the CD4+ CD25highFOXP3+ T-lymphocytes that mediate neuroprotection by suppressing proinflammatory responses. However, Treg suppressive functions are impaired in ALS, but are restored and even enhanced following expansion ex vivo. Autologous infusions of these expanded T regs together with subcutaneous IL- 2 injections formed the basis of two ALS clinical trials. In a Phase 1 pilot study of 3 ALS patients, infusions were safe and well-tolerated and slowed progression rates during early and later stages of the disease. Treg numbers and suppressive function increased after each infusion and correlated with slowing of disease progression. However, the duration of the clinical benefit was limited, possibly related to the serum biomarkers of oxidative stress, 4-hydroxynonenal, and oxidized LDL These lipid peroxide biomarkers were increased prior to Treg infusions, fell with Treg infusions and slowing of disease progression, rose again as disease progression accelerated in the absence of infused Tregs, then fell again when Tregs were reinfused. Thus, the levels of 4-HNE and ox- LDL were effectively responsive to Treg infusions and mirrored the stabilization or deterioration of the subject's clinical status. A Phase 2A study of autologous infusion of expanded Tregs in combination with subcutaneous IL-2 injections was undertaken at Houston Methodist and Massachusetts General Hospitals. The study was planned for 12 ALS pts enrolled in a 24-week randomized control trial (RCT) followed by a 24- week open label extension (OLE). In the RCT Treg/IL-2 treatments were safe and well-tolerated;with increased Treg suppressive function in the active group. Evaluation of relative progression rates in the RCT was precluded by the COVID pandemic which decreased the number of participants. However, 8 ALS patients did complete the 24-week OLE;Treg/IL-2 treatments were safe and well-tolerated, and Treg suppressive function and numbers were increased. Six patients showed slow to no progression in the OLE (mean change of -2.7 points on ALSFRS-R) Two patients progressed rapidly;they were unresponsive to Treg infusions and had elevated markers of peripheral inflammation (IL-17C and IL-17F) as well as elevated markers of oxidative stress (OLR1 and oxidized-LDL). The 6 participants in the slow progressing group had normal levels. Whether Treg/IL-2 treatments can slow disease progression in ALS requires a large double-blind randomized controlled study. Nevertheless, our open-label studies, albeit in a limited population, suggest that Treg therapy is safe and well tolerated, and a promising approach to slowing ALS progression;lipid peroxide biomarkers may not only reflect a heightened pro-inflammatory milie","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"1 - 31"},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41647546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theme 11 - Cognitive and Psychological Assessment and Support","authors":"M. Metzger, V. Sirenko, E. Giglia, P. Mehra, Y. Tadjine, S. Bista, N. Pender, P. Ferraro, E. Gervino, G. Meo, M. Cillerai, M. Pardini, L. Roccatagliata, A. Schenone, C. Caponnetto","doi":"10.1080/21678421.2022.2120687","DOIUrl":"https://doi.org/10.1080/21678421.2022.2120687","url":null,"abstract":"Background: Stress and dysphoria often follow the diagnosis MND, with some adapting quickly and finding a new balance, while others struggle to come to terms with the diagnosis and continue experiencing high levels of emotional distress. As observed in our previous study in patients with MND and their partners, re-appraisal and finding meaning play a significant role in the process of psychological adjustment. Psychological counselling can be offered to those in need, but is often not available or not specifically enough. Meaning Centred Psychotherapy: Breitbart ’ s Meaning Centred Psychotherapy (BMCP) has been found to be well- accepted and effective in advanced cancer patients. BMCP is a time-limited, manualized group psychotherapy, focusing on sense of meaning and thereby relieving distress and promoting psychological well-being and it has been proven effective in multiple RCT ’ s, also in the Netherlands. Most themes addressed in BMCP seem in clinical practice also suitable for MND patients, who are faced with similar complex issues related to the prospect of progressive physical decline and early death. Patients are supported and guided in a directive manner to focus on what is meaningful to them - by reflect-ing on their life and to thereby gaining sharper focus on what is important to them in the remaining time ahead of them. To date, BMCP has not been studied in MND patients. Physical barriers can be overcome by offering this therapy individually and online, where patients follow the pro- gramme from home with e-mail coaching and face to face video-consulting with the psychologist. Methods: We have adapted the Dutch group protocol for the purpose of such an online approach specifically for individuals diagnosed with ALS or PMA patients and this resulted in the Making Sense training. At this moment we are testing acceptability, feasibility and patient satisfaction, while we document changes in distress over time. We hypothesize that offering 8-weeks the internet-based Making Sense training for distressed MND patients, is acceptable, feasible and helpful in reducing emotional MND related distress with sub-sequent improvement in quality of life. A mixed method approach, collecting both quantitative and qualitative data, is used. For pragmatic and ethical reasons, we chose the best alternative for the RCT design namely a randomized Single-Case Experimental (SCE) design that requires only a small sample (N ¼ 5). This study aims to answer the following questions: 1. Is the Making Sense training acceptable, feasible and appreciated by patients with MND? 2. What are the effects on emotional MND related distress (primary outcome), perceived quality of life and sense of meaning (second- ary outcomes)? Results: At this moment three patients are included and started the training. Two new participants will be included and randomised soon. We will be able to present our first results in December 2022. Background: ALS primarily affects motor functions, ","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"167 - 175"},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45168372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theme 06 - Tissue Biomarkers","authors":"N. Gaur, M. Wang, R. Steinbach, H. Riemenschneider, D. Edbauer, M. Plaas, O. Witte, M. Brill, J. Grosskreutz, Monteiro Lopes, V. A. Conceiç, C. S. Lopes, M. Gromicho, N. C. Santos, F. A. Carvalho, M. D. Carvalho, A. Pronto-Laborinho","doi":"10.1080/21678421.2022.2120682","DOIUrl":"https://doi.org/10.1080/21678421.2022.2120682","url":null,"abstract":"Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a variable clinical presenta- tion and rate of disease progression. There is no coherent strategy to develop disease biomarkers for early diagnosis in atypical cases or for phenotypic stratification. Several proteomic studies on affected tissues and fluids from ALS individu-als have recently emerged. Beside target-driven approaches to identify biomarkers, as shown for neurofilaments, an unbiased methodology to mine the wealth of these prote- omic data studies could dissect the best candidate biomarkers for validation in ALS biofluids (1). Objectives: To build a comprehensive dataset incorporating proteomic studies from tissues and biofluids collected from patients with ALS that could serve as testbed for a bioinfor- matic analysis and for the identification of a molecular signature of the disease. To analyse bioinformatically available datasets and identify an ALS proteomic signature that can guide further investigations into informative biomarkers in biological fluids. Methods: ALS Mass spectrometry and SomaScan data from a range of human studies fulfilling pre-defined selection criteria have been collected from publicly available repositories. Data integration relies on overcoming limitations intrinsic to these heterogeneous datasets, including accessibility, study size, data representation and tissue type. Datasets are individually ana- lysed with comprehensive bioinformatics including principal component analysis and data clustering. Once proteins with a disease-specific pattern of expression are identified within different study populations in silico, validation of their utility as biomarkers will be undertaken on our longitudinal ALS samples. Results: The first part of the project has focused on data col-lection, evaluation and cleaning. From 81 ALS studies, 13 human tissue/fluid and 12 cell lines studies have been selected for analyses. 30 of the 81 studies do not provide supplementary information and 9 have shared only signifi- cant discoveries. At this stage of the project, volcano plots and heat maps have been used to aid proteomics biomarkers visualisation. Compared to controls proteins levels, MMP-9, OLR, Calgranulin B, and S100A6 genes have been differen-tially regulated across some of the ALS studies. Discussion: There are limited publicly available data which are difficult to access. Most of the information found in the literature is about finite results but not raw data. As expected, there is not an established shared template to col-lect Mass spectrometry data, complicating data comparison and analysis. However, we have built a dataset that encom-passes tissue/biofluids and cell lines which shows promising results. Our work is currently in progress but it is expected to deliver potentially novel protein candidates that may have a role as ALS biomarkers and could be tested in our large lon- gitudinal biofluids collection. Results: Approximat","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"99 - 109"},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44901392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theme 08 - Clinical Imaging and Electrophysiology","authors":"M. Abidi, P. Pradat, N. Termoz, A. Couillandre, P. Bede, G. D. Marco, -. S.Borrego, Ecija, J. van, Swieten, L. Jiskoot, F. Moreno, R. Laforce, C. Graff, M. Masellis, M. Tartaglia, J. Row, B. Borroni, E. Finger, M. Synofzik, D. Galimberti, R. Vanderberghe, A. de, Mendonça, A. Ferhard, S. Ducharme, I. Ber, I. Santana, F. Pasquier, J. Levin, S. Sorbi, P. Tiraboschi, H. Seelaar, T. Langheinrich, J. Rohrer, R. Sala-Llonch, anchez-Valle","doi":"10.1080/21678421.2022.2120684","DOIUrl":"https://doi.org/10.1080/21678421.2022.2120684","url":null,"abstract":"Background: The functional reorganization of brain networks sustaining gait is poorly characterized in amyotrophic lateral sclerosis (ALS) despite ample evidence of progressive discon- nection between brain regions. Objectives: The main objective of this fMRI study is to assess gait imagery-specific networks in ALS patients using dynamic causal modelling (DCM) complemented by parametric empir-ical Bayes (PEB) framework. Methods: Seventeen lower motor neuron predominant (LMNp) ALS patients, fourteen upper motor neuron predominant (UMNp) ALS patients and fourteen healthy controls par- ticipated in this study. Each subject performed a dual motor imagery task: normal and precision gait. The Movement Imagery Questionnaire (MIQ-rs) and imagery time (IT) were used to evaluate gait imagery in each participant. In a neuro-biological computational model, the circuits involved in imagined gait and postural control were investigated by modelling the relationship between normal/precision gait and connection strengths. Results: Behavioral results showed significant increase in IT in UMNp patients compared to healthy controls ( p corrected < 0.05) and LMNp ( p corrected < 0.05). During precision gait, healthy controls activate the model ’ s circuits involved in the imagined gait and postural control. In UMNp, decreased con- nectivity (inhibition) from basal ganglia (BG) to supplemen-tary motor area (SMA) and from SMA to posterior parietal cortex (PPC) is observed. Contrary to healthy controls, DCM detects no cerebellar-PPC connectivity in neither UMNp nor LMNp ALS. During precision gait, bilateral connectivity (excit- ability) between SMA and BG is observed in the LMNp group contrary to UMNp and healthy controls. Discussion: Our findings demonstrate the utility of imple-menting both DCM and PEB to characterize connectivity patterns in specific patient phenotypes. Our approach enables the identification of specific circuits involved in postural deficits, and our findings suggest a putative excitatory – inhibitory imbalance. More broadly, our data demonstrate how clinical manifestations are underpinned by network-specific discon- nection phenomena in ALS. Background: The C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD) and/or motor neuron disease (MND). Corticospinal degeneration has been described in post-mortem neuropathological studies in these patients, especially in those with MND. Objectives: We used MRI to analyze white matter (WM) vol-umes in presymptomatic and symptomatic C9orf72 expan- sion carriers and investigated whether its measure may be helpful in predicting the onset of symptoms. Methods: We studied 102 presymptomatic C9orf72 mutation carriers, 52 symptomatic carriers: 42 suffering from FTD and 11 from MND, and 75 non-carriers from the Genetic Frontotemporal dementia Initiative (GENFI). All subjects underwent T1-MRI acquisition. We used FreeSurfer to estimate the volume proportion of WM in the brainstem regions ","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"125 - 132"},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48540912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theme 07 - Pre-Clinical Therapeutic Strategies","authors":"E. Obrador, R. Salvador-Palmer, J. Estrela, P. Moreno-Murciano, M. Oriol-Caballo, opez-Blanch, M. Baird, J. Caporale, H. Girard, A. Reed, F. Roussel, M. Schwartz, K. Faulconer, S. Likhite, K. Meyer","doi":"10.1080/21678421.2022.2120683","DOIUrl":"https://doi.org/10.1080/21678421.2022.2120683","url":null,"abstract":"Background and method: Oxidative stress and neuroinflam- mation pave the way leading to neurodegeneration in amyotrophic lateral sclerosis (ALS) (1). Astrogliosis, increased levels of proinflammatory cytokines in the cerebrospinal fluid, and lower GSH content in the motor cortex are associated with ALS progression (1 – 3). Thus, we propose supplementation with N-acetylcysteine (GSH precursor), nicotinamide riboside (NR, a NAD þ promoter) and pterostilbene (PT, a natural antioxidant) could help to slow down the progression of the dis- ease (4,5). Results: NR and PT treatment was efficacious in ALS patients in a pilot human clinical trial (NCT03489200). Following 4 months of treatment (4): a 2.5-point a (cid:2) placebo. Discussion: Combined treatment ameliorated TNF a -induced oxidative stress and motor neuron death in vitro and decreased the microgliosis and astrogliosis associated with ALS progression. Our results support the involvement of oxidative stress, specific Nrf2-dependent antioxidant defenses, motor function in ALS mouse models and greatly extends their lifespan. As AAV9 does not efficiently target nor correct ALS microglia, despite neuron and astrocyte correction, the ALS mice still die of the disease at later time points with extensive microgliosis observed at the end stage. Therefore, it is evident that to provide the best therapeutic outcome for ALS patients, treatments that simultaneously target motor neurons, astrocytes, and microglia are necessary. Objective: To design and evaluate combination treatment approaches targeting neuronal and non-neuronal cells to reach improved therapeutic outcome in the treatment of ALS. Methods: In this currently ongoing study, we test multiple approaches combining our previously developed AAV9 mediated SOD1 downregulation approach in tandem with microglial modulation using ablation or immune modulation. Utilizing this combinatory approach, we indirectly target microglia, thereby dampening the chronic neuroinflammation in ALS mice in add- ition to downregulation of mutant SOD1 in motor neurons and astrocytes. We compare the combination approach against single treatment of SOD1 downregulation, microglia modulations, and untreated controls. Motor function is tested by rotarod performance and grip strength assessments twice per week. Disease onset, duration, and survival are monitored and compared to appropriate controls. Results: Our study shows that SOD1 downregulation in com- bination with small molecule mediated microglia ablation does not have a beneficial synergistic effect, while a novel AAV9 based combination treatment of SOD1 downregulation and a microglial immune modulation transgene lead to significantly longer survival and delayed disease onset of SOD1G93A mice compared to either single treatment. survey caregiver Statistical analyses included frequencies, per- centages, means, medians, and chi-square. Results: The seventy-six participants were caregivers (57%) and people living with neurol","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"110 - 124"},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46587421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Table of Contents - Poster Communications","authors":"","doi":"10.1080/21678421.2022.2082740","DOIUrl":"https://doi.org/10.1080/21678421.2022.2082740","url":null,"abstract":"","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"(i) - (i)"},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45010868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theme 05 - Human Cell Biology and Pathology (including iPSC studies)","authors":"K. Smith, S. Edassery, M. Garjani, Y. Li, C. Williams, E. Daley, T. Hark, S. Marklund, L. Ostrow, J. Gilthorpe, J. Ichida, R. Kalb, J. Savas, E. Kiskinis, N. Grima, C. Shephard, D. Rowe, M. Kiernan, S. Mazumder, I. Blair, K. Williams","doi":"10.1080/21678421.2022.2120681","DOIUrl":"https://doi.org/10.1080/21678421.2022.2120681","url":null,"abstract":"Background: TDP-43 pathology is the hallmark of ALS found in 98% of cases. While mutations in the gene encoding TDP43, TARDBP, are a rare cause of ALS, the deposition of TDP-43 positive cytoplasmic inclusions remains a common neuropath- ology for the majority of cases. Recent reports have shown that mitochondrial dysfunction plays a significant role in motor neuron degeneration in ALS and TDP-43 was found to modu- late several mitochondrial transcripts. Identifying dysfunctional mitochondrial pathways in neurons from TDP-43 patients would significantly contribute to our understanding of disease mechanisms and potential new therapeutic targets. Objectives: The aim of this study is to determine how TDP- 43 mutations affect mitochondrial function and intracellular transport using iPS-derived MNs from patients. Methods: In this study, we differentiated patient motor neurons derived from induced pluripotent stem cells (iPSCs) carrying mutations in TDP-43 (M337V and I383T). Seahorse XFe was used to assess mitochondrial respiration, ATP production and spare respiratory capacity and live calcium imaging was used to determine mitochondrial calcium buffering. Neurons were grown on microfluidic chambers for studying axonal transport and MitoTracker movement was quantified during live imaging in the microgrooves. Results: We found that TDP-43-M337V and TDP-43-I383T MNs show reduced mitochondrial basal respiration and ATP production at baseline and reduced spare respiratory capacity when ER stress was induced by thapsigargin. Furthermore, we also detect significantly reduced mitochondrial length and surface area in patient iPS-MNs, indicating increased fragmentation. RNA sequencing and immunoblot- ting confirmed that mutant TDP-43 modulated the expression of key molecules involved in ATP production and respiration, such as ATP synthase and COX5A. Moreover, colocalization studies showed that TDP-43 directly binds to ATPB. Imaging of axonal transport revealed reduced speed of retrograde mitochondrial transport in TDP-43-M337V and TDP-43-I383T as well as reduced endosomal transport, which correlated with an imbalance of motor proteins, such as KIF5A, DNAH and dynactin-1. Conclusions: This study shows that ALS iPS-derived MNs with mutations in TDP-43 have deficiencies in essential mitochondrial functions, such as respiration and ATP production, as well as reduced intracellular transport of mitochondria and endosomes. and altered lipid are of amyotrophic laterals sclerosis (ALS) and critical components of ALS disease pathology. In healthy individuals, inflammation is resolved through the Methods: We used flow cytometry in combination with a cus-tomized panel to profile monocytes in peripheral blood mono-nuclear cells from ALS patients at three-time points ( n at visit 1 ¼ 40, n at visit 2 ¼ 18 and n at visit 3 ¼ 12). We used unsuper-vised clustering methods to identify monocyte cell populations. Differential state analysis was performed comparing the FPRL1 abundan","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"83 - 98"},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44687875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theme 01 - Epidemiology and Informatics","authors":"J. Barberio, C. Lally, V. Kupelian, W. Flanders, A. Berger, M. Locatelli, M. Quintana, A. Kalmes, S. Paganoni, A. Sherman, V. Hodgkinson, G. Jewett, A. Abrahao, N. Koenig, A. Dyck, T. Benstead, H. Briemberg, M. Chum, N. Dupré, A. Genge","doi":"10.1080/21678421.2022.2120677","DOIUrl":"https://doi.org/10.1080/21678421.2022.2120677","url":null,"abstract":"The incidence of amyotrophic lateral sclerosis in Ohio 2016-2018: the Ohio population-based ALS Registry. Environmental and occupational risk factors of amyotrophic lateral sclerosis: a population-based case-control study. Risk factors associated with mortality among patients with COVID-19 in intensive care units in Lombardy, Italy. [Extracted from the article]","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"32 - 39"},"PeriodicalIF":2.8,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43999326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALSUntangled #64: butyrates","authors":"Yuyao Sun, R. Bedlack, C. Armon, Morgan Beauchamp, T. Bertorini, R. Bowser, M. Bromberg, J. Caress, Gregory T. Carter, J. Crayle, M. Cudkowicz, J. Glass, Carlayne Jackson, Isaac Lund, Sarah Martin, S. Paganoni, G. Pattee, Dylan Ratner, Kristiana Salmon, Paul Wicks","doi":"10.1080/21678421.2022.2045323","DOIUrl":"https://doi.org/10.1080/21678421.2022.2045323","url":null,"abstract":"Abstract ALSUntangled reviews alternative and off-label treatments for people living with amyotrophic lateral sclerosis (PALS). Here we review butyrate and its different chemical forms (butyrates). Butyrates have plausible mechanisms for slowing ALS progression and positive pre-clinical studies. One trial suggests that sodium phenylbutyrate (NaPB) in combination with Tauroursodeoxycholic acid (TUDCA) can slow ALS progression and prolong survival, but the specific contribution of NaPB toward this effect is unclear. Butyrates appear reasonably safe for use in humans. Based on the above information, we support a trial of a butyrate in PALS, but we cannot yet recommend one as a treatment.","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"23 1","pages":"638 - 643"},"PeriodicalIF":2.8,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44882279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Table of Contents - Poster Communications","authors":"","doi":"10.1080/21678421.2021.1985785","DOIUrl":"https://doi.org/10.1080/21678421.2021.1985785","url":null,"abstract":"","PeriodicalId":7740,"journal":{"name":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration","volume":"22 1","pages":"(i) - (i)"},"PeriodicalIF":2.8,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47861725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}