31,568 results match your criteria Amyotrophic Lateral Sclerosis


A phase I/IIa clinical trial of autologous hematopoietic stem cell transplantation in amyotrophic lateral sclerosis.

J Neurol 2022 May 21. Epub 2022 May 21.

Department of Neurosciences, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.

Objective: To verify the safety and potential effect on ALS progression of a low-intensity immunosuppressive regimen followed by autologous hematopoietic stem cell transplantation (aHSCT) in amyotrophic lateral sclerosis (ALS) patients.

Methods: ALS eligible patients underwent a set of clinical and laboratory evaluations at T-4 (screening), T-1 (pre-treatment visit), and for the 12 consecutive months after treatment (T3, T6, T9, T12). We evaluated the tolerability of the procedure, its efficacy on clinical course and quality of life (QoL). Read More

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Rummeliibacillus suwonensis: First Time Isolation from Human Feces by Culturomics.

Curr Microbiol 2022 May 20;79(7):197. Epub 2022 May 20.

Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Gut microbiota is a complex ecosystem composed by trillions of microorganisms that are crucial for human health or disease status. Currently, there are two methodological options to explore its complexity: metagenomics and culturomics. Culturomics is an approach that uses multiple culture conditions (days of incubation, enrichment factors and growth temperature) and MALDI-TOF mass spectrometry for the identification of bacterial species and sequencing when this method fails. Read More

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Bidirectional Mendelian randomization to explore the causal relationships between Sleep traits, Parkinson's disease and Amyotrophic lateral sclerosis.

Sleep Med 2022 Apr 19;96:42-49. Epub 2022 Apr 19.

School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Objective: Sleep disturbances have been linked with Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) in observational studies, and the comorbidity of PD and ALS has been reported in clinical case reports, but the causalities remain unclear. This study aims to examine bidirectional causal relationships between sleep traits, PD and ALS.

Methods: Bidirectional two sample Mendelian randomisation (MR) analyses were conducted, with data from individuals of mainly European ancestry. Read More

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Genetic and pharmacological PARP inhibition reduces axonal degeneration in C. elegans models of ALS.

Hum Mol Genet 2022 May 20. Epub 2022 May 20.

Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.

Axonal degeneration is observed in early stages of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). This degeneration generally precedes apoptosis and therefore may be a promising therapeutic target. An increasing number of genes have been identified to actively regulate axonal degeneration and regeneration, however, only a few potential therapeutic targets have been identified in the context of neurodegenerative diseases. Read More

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Mild motor impairment as prodromal state in amyotrophic lateral sclerosis: a new diagnostic entity.

Brain 2022 May 20. Epub 2022 May 20.

Department of Neurology, University of Miami, Miami, FL, USA.

Amyotrophic lateral sclerosis (ALS), when viewed as a biological entity rather than a clinical syndrome, likely evolves along a continuum, with the initial clinically silent phase eventually evolving into clinically manifest ALS. Since motor neuron degeneration is incremental and cumulative over time, it stands to reason that the clinical syndrome of ALS is likely preceded by a prodromal state characterized by minor motor abnormalities that are initially insufficient to permit a diagnosis of ALS. This prodromal period, however, is usually missed, given the invariably long delays between symptom onset and diagnostic evaluation. Read More

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Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases.

Eur Radiol 2022 May 20. Epub 2022 May 20.

Molecular Medicine Unit, IRCCS Fondazione Stella Maris, Pisa, Italy.

Objectives: Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative diseases characterised by upper motor neuron (UMN) impairment of the lower limbs. The differential diagnosis with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) can be challenging. As microglial iron accumulation was reported in the primary motor cortex (PMC) of ALS cases, here we assessed the radiological appearance of the PMC in a cohort of HSP patients using iron-sensitive MR imaging and compared the PMC findings among HSP, PLS, and ALS patients. Read More

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Associations of self-reported occupational exposures and settings to ALS: a case-control study.

Int Arch Occup Environ Health 2022 May 20. Epub 2022 May 20.

Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA.

Background: Environmental exposures contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal and progressive neurological disease. Identification of these exposures is important for targeted screening and risk factor modification.

Objective: To identify occupational exposures that are associated with a higher risk of ALS using both survey and standard occupational classification (SOC) coding procedures, and to highlight how exposure surveys can complement SOC coding. Read More

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Treatment for sialorrhea (excessive saliva) in people with motor neuron disease/amyotrophic lateral sclerosis.

Cochrane Database Syst Rev 2022 May 20;5:CD006981. Epub 2022 May 20.

The Walton Centre NHS Foundation Trust, Liverpool, UK.

Background: Motor neuron disease (MND), also known as amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative condition that may cause dysphagia, as well as limb weakness, dysarthria, emotional lability, and respiratory failure. Since normal salivary production is 0.5 L to 1. Read More

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Genetic and Epigenetic Interplay Define Disease Onset and Severity in Repeat Diseases.

Front Aging Neurosci 2022 3;14:750629. Epub 2022 May 3.

Center for Systems and Therapeutics, Gladstone Institutes, San Francisco, CA, United States.

Repeat diseases, such as fragile X syndrome, myotonic dystrophy, Friedreich ataxia, Huntington disease, spinocerebellar ataxias, and some forms of amyotrophic lateral sclerosis, are caused by repetitive DNA sequences that are expanded in affected individuals. The age at which an individual begins to experience symptoms, and the severity of disease, are partially determined by the size of the repeat. However, the epigenetic state of the area in and around the repeat also plays an important role in determining the age of disease onset and the rate of disease progression. Read More

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Neuroimmune Crosstalk Between the Peripheral and the Central Immune System in Amyotrophic Lateral Sclerosis.

Front Aging Neurosci 2022 3;14:890958. Epub 2022 May 3.

Department of Neurology, Peking University Third Hospital, Beijing, China.

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the degeneration and death of motor neurons. Systemic neuroinflammation contributes to the pathogenesis of ALS. The proinflammatory milieu depends on the continuous crosstalk between the peripheral immune system (PIS) and central immune system (CIS). Read More

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Preclinical evaluation of WVE-004, aninvestigational stereopure oligonucleotide forthe treatment of -associated ALS or FTD.

Mol Ther Nucleic Acids 2022 Jun 20;28:558-570. Epub 2022 Apr 20.

Wave Life Sciences, 733 Concord Avenue, Cambridge, MA 02138, USA.

A large hexanucleotide (GC) repeat expansion in the first intronic region of is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Several mechanisms have been proposed to explain how the repeat expansion drives disease, and we hypothesize that a variant-selective approach, in which transcripts affected by the repeat expansion are preferentially decreased, has the potential to address most of them. We report a stereopure antisense oligonucleotide, WVE-004, that executes this variant-selective mechanism of action. Read More

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Integrating functional genomics with genetics to understand the biology of ALS and FTD.

Authors:
Carlos Cruchaga

Med (N Y) 2022 Apr;3(4):226-227

Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, MO, USA; The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:

Genetic variants in chromosome 19 are strongly associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Ma et al. and Brown et al. Read More

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Poly(GR) and poly(GA) in cerebrospinal fluid as potential biomarkers for C9ORF72-ALS/FTD.

Nat Commun 2022 May 19;13(1):2799. Epub 2022 May 19.

Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA.

GGGGCC repeat expansion in C9ORF72, which can be translated in both sense and antisense directions into five dipeptide repeat (DPR) proteins, including poly(GP), poly(GR), and poly(GA), is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we developed sensitive assays that can detect poly(GA) and poly(GR) in the cerebrospinal fluid (CSF) of patients with C9ORF72 mutations. CSF poly(GA) and poly(GR) levels did not correlate with age at disease onset, disease duration, or rate of decline of ALS Functional Rating Scale, and the average levels of these DPR proteins were similar in symptomatic and pre-symptomatic patients with C9ORF72 mutations. Read More

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Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM.

Nat Commun 2022 May 19;13(1):2776. Epub 2022 May 19.

RNA Therapeutics Institute, UMass Chan Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.

Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two DPR proteins, poly-PR and poly-GR, repress cellular translation but the molecular mechanism remains unknown. Here we show that poly-PR and poly-GR of ≥20 repeats inhibit the ribosome's peptidyl-transferase activity at nanomolar concentrations, comparable to specific translation inhibitors. Read More

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Understanding the contributions of VPS35 and the retromer in neurodegenerative disease.

Neurobiol Dis 2022 May 16;170:105768. Epub 2022 May 16.

Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA. Electronic address:

Perturbations of the endolysosomal pathway have been suggested to play an important role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD). Specifically, VPS35 and the retromer complex play an important role in the endolysosomal system and are implicated in the pathophysiology of these diseases. A single missense mutation in VPS35, Asp620Asn (D620N), is known to cause late-onset, autosomal dominant familial PD. Read More

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Why you always in a mood? Pumpin' polyP, actin' brand new.

Neuron 2022 May;110(10):1603-1605

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address:

What causes neurons to die in neurodegenerative disease? In this issue of Neuron, Arredondo et al., 2022 report an unexpected culprit that may drive neuronal death in amyotrophic lateral sclerosis-an evolutionarily ancient energy-storage polymer called polyphosphate (polyP). Read More

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Sleep, Pain, and Neurodegeneration: A Mendelian Randomization Study.

Front Neurol 2022 2;13:765321. Epub 2022 May 2.

Centre for Genetic Epidemiology, Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.

Our aim was to determine whether the genetic liability to sleep and pain-related traits have a causal effect on risk of neurodegeneration in individuals of predominantly European ancestry. We selected five neurodegenerative disorders, namely, age-related macular degeneration (AMD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson's disease (PD). Sleep duration (SD), short sleep (SS), long sleep (LS), chronotype (CHR), morning person (MP), insomnia (INS), and multisite chronic pain (MCP) were considered as exposures. Read More

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Utility of the ALSFRS-R for Predicting ALS and Comorbid Disease Neuropathology: The Veterans Affairs Biorepository Brain Bank.

Muscle Nerve 2022 May 18. Epub 2022 May 18.

VA Boston Healthcare System, Boston, MA.

Introduction/aims: The amyotrophic lateral sclerosis (ALS) functional rating scale-revised (ALSFRS-R) is commonly used to track ALS disease progression; however, there are gaps in the literature regarding the extent to which ALSFRS-R relates to underlying central nervous system (CNS) pathology. The current study explored the association between ALSFRS-R (total and subdomain) scores and postmortem neuropathology (both ALS-specific and comorbid disease).

Methods: We utilized hierarchical cluster analysis (HCA) conducted using ALSFRS-R subdomain scores to identify profiles of motor dysfunction within our sample of 93 military veterans with autopsy-confirmed ALS. Read More

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Efficacy and safety of Lenzumestrocel (Neuronata-R® inj.) in patients with amyotrophic lateral sclerosis (ALSUMMIT study): study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial.

Trials 2022 May 18;23(1):415. Epub 2022 May 18.

Department of Neurology, Hanyang University Hospital, Seoul, South Korea.

Background: A single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS.

Methods: ALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. Read More

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Design of a Randomized, Placebo-Controlled, Phase 3 Trial of Tofersen Initiated in Clinically Presymptomatic SOD1 Variant Carriers: the ATLAS Study.

Neurotherapeutics 2022 May 18. Epub 2022 May 18.

Biogen, 225 Binney Street, Cambridge, MA, 02142, USA.

Despite extensive research, amyotrophic lateral sclerosis (ALS) remains a progressive and invariably fatal neurodegenerative disease. Limited knowledge of the underlying causes of ALS has made it difficult to target upstream biological mechanisms of disease, and therapeutic interventions are usually administered relatively late in the course of disease. Genetic forms of ALS offer a unique opportunity for therapeutic development, as genetic associations may reveal potential insights into disease etiology. Read More

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Accumulation of misfolded SOD1 outlines distinct patterns of motor neuron pathology and death during disease progression in a SOD1 mouse model of amyotrophic lateral sclerosis.

Brain Pathol 2022 May 18. Epub 2022 May 18.

Patologia Neuromuscular Experimental, Departament de Medicina Experimental, Facultat de Medicina, Universitat de Lleida and Institut de Recerca Biomèdica de Lleida (IRBLleida), Lleida, Catalonia, Spain.

Early misfolded superoxide dismutase 1 (mfSOD1) accumulation, motor neuron (MN) degeneration, and microgliosis are hallmark pathological features in SOD1 amyotrophic lateral sclerosis (ALS) mice. Because of the different vulnerabilities of distinct MN subtypes, degenerating and surviving MNs coexist in different proportions during disease progression. By examining the expression of misfolded conformers of SOD1 using specific antibodies, we defined distinct MN phenotypes that were evaluated during disease progression and the local neuroinflammatory reaction. Read More

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Distribution Changes of Neural Precursor Cells in the Brain Stem of Tg(SOD1*G93A)1Gur Mice.

Neurodegener Dis 2022 May 18. Epub 2022 May 18.

Objectives: The alteration of vimentin-containing cells (VCCs) proliferation, differentiation and migration in the brain stem of amyotrophic lateral sclerosis (ALS)-like transgenic mice (Tg(SOD1*G93A)1Gur mice) (TG mice) and wild-type mice (WT mice) at the different disease stages of TG mice were studied in this study. The aim of this study was to investigate the change features of proliferation, differentiation and migration of endogenous neural precursor cells (NPCs) and to explore the potential effects of NPCs on restoring degenerated neurons in ALS.

Methods: The proliferation, differentiation and migration of VCCs in both different anatomic regions and neural cells of brain stem at the different stages including pre-onset (60-70 days), onset (90-100 days) and progression (120-130 days) stages of TG mice and in WT mice (control) were examined using the immunofluorescence technology. Read More

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Alterations in metabolic biomarkers and their potential role in amyotrophic lateral sclerosis.

Ann Clin Transl Neurol 2022 May 18. Epub 2022 May 18.

Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

Background: Metabolic dysfunction has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS). This study aimed to investigate the potential role of metabolic biomarkers in the progression of ALS and understand the possible metabolic mechanisms.

Methods: Fifty-two patients with ALS and 24 normal controls were included, and blood samples were collected for analysis of metabolic biomarkers. Read More

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Heat shock protein Grp78/BiP/HspA5 binds directly to TDP-43 and mitigates toxicity associated with disease pathology.

Sci Rep 2022 May 17;12(1):8140. Epub 2022 May 17.

Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, 85724, USA.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no cure or effective treatment in which TAR DNA Binding Protein of 43 kDa (TDP-43) abnormally accumulates into misfolded protein aggregates in affected neurons. It is widely accepted that protein misfolding and aggregation promotes proteotoxic stress. The molecular chaperones are a primary line of defense against proteotoxic stress, and there has been long-standing interest in understanding the relationship between chaperones and aggregated protein in ALS. Read More

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Nuclear RNA transcript levels modulate nucleocytoplasmic distribution of ALS/FTD-associated protein FUS.

Sci Rep 2022 May 17;12(1):8180. Epub 2022 May 17.

Department of Biological Sciences, Columbia University, New York, NY, 10027, USA.

Fused in Sarcoma (FUS) is a nuclear RNA/DNA binding protein that mislocalizes to the cytoplasm in the neurodegenerative diseases ALS and FTD. Despite the existence of FUS pathogenic mutations that result in nuclear import defects, a subset of ALS/FTD patients display cytoplasmic accumulation of wild-type FUS, although the underlying mechanism is unclear. Here we confirm that transcriptional inhibition, specifically of RNA polymerase II (RNAP II), induces FUS cytoplasmic translocation, but we show that several other stresses do not. Read More

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Development of an endogenously myc-tagged TARDBP (TDP-43) zebrafish model using the CRISPR/Cas9 system and homology directed repair.

Comp Biochem Physiol B Biochem Mol Biol 2022 May 14;261:110756. Epub 2022 May 14.

Department of Neurology and Neurosurgery, Montreal Neurological Institute, Faculty of Medicine, McGill University. Electronic address:

Many of the modern advances in cellular biology have been made by the expression of engineered constructs with epitope tags for subsequent biochemical investigations. While the utility of epitope tags has permitted insights in cellular and animal models, these are often expressed using traditional transgenic approaches. Using the CRISPR/Cas9 system and homology directed repair we recombine a single myc epitope sequence following the start codon of the zebrafish ortholog of TARDBP (TDP-43). Read More

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Can We Treat Neurodegenerative Proteinopathies by Enhancing Protein Degradation?

Mov Disord 2022 May 17. Epub 2022 May 17.

Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.

Neurodegenerative proteinopathies are defined as a class of neurodegenerative disorders, with either genetic or sporadic age-related onset, characterized by the pathological accumulation of aggregated protein deposits. These mainly include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) as well as frontotemporal lobar degeneration (FTLD). The deposition of abnormal protein aggregates in the brain of patients affected by these disorders is thought to play a causative role in neuronal loss and disease progression. Read More

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Hastening the Diagnosis of Amyotrophic Lateral Sclerosis.

Neurology 2022 May 16. Epub 2022 May 16.

Department of Neurology, Pensylvania State University, Hershy, PA.

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neurodegenerative disease. Neurologists generally see patients as requested and as schedules allow. This practice is part of the reason it takes approximately 12 months from onset of new progressive weakness to receive a definitive diagnosis of ALS. Read More

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Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial.

J Neurol Neurosurg Psychiatry 2022 May 16. Epub 2022 May 16.

Neurology Associates, Lincoln, Nebraska, USA.

Background: Coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS).

Objective: Determine whether PB/TURSO prolonged tracheostomy/ventilation-free survival and/or reduced first hospitalisation in participants with ALS in the CENTAUR trial.

Methods: Adults with El Escorial Definite ALS ≤18 months from symptom onset were randomised to PB/ TURSO or placebo for 6 months. Read More

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