How the prospect of a clinical trial impacts decision-making for predictive genetic testing in ALS.

Genetic testing practices are rapidly evolving for people living with, or at-risk for, amyotrophic lateral sclerosis (ALS), due to emerging genotype-driven therapies. This study explored how individuals at-risk for familial ALS (fALS) perceive the opportunity to participate in a clinical trial, and to better understand how that may influence the decision-making process for predictive genetic testing. This study used both quantitative and qualitative data analyses.

Safety and tolerability of tegoprubart in patients with amyotrophic lateral sclerosis: A Phase 2A clinical trial.

Background: The interaction of CD40L and its receptor CD40 on activated T cells and B cells respectively control pro-inflammatory activation in the pathophysiology of autoimmunity and transplant rejection. Previous studies have implicated signaling pathways involving CD40L (interchangeably referred to as CD154), as well as adaptive and innate immune cell activation, in the induction of neuroinflammation in neurodegenerative diseases. This study aimed to assess the safety, tolerability, and impact on pro-inflammatory biomarker profiles of an anti CD40L antibody, tegoprubart, in individuals with amyotrophic lateral sclerosis (ALS).

How to break the news in amyotrophic lateral sclerosis/motor neuron disease: practical guidelines from experts.

In amyotrophic lateral sclerosis/motor neuron disease (ALS/MND), it is necessary to communicate difficult news during the initial diagnosis and throughout the disease trajectory as the condition progresses. However, delivering difficult news to people with ALS/MND is an emotionally demanding task for healthcare and allied health professionals-one for which many feel ill-prepared because of limited training in this area. Ineffective communication of difficult news damages the patient-provider relationship and negatively impacts patient quality of life (QoL).

Temporal and spatial progression of microstructural cerebral degeneration in ALS: A multicentre longitudinal diffusion tensor imaging study.

Objective: The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS.

Methods: The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2).

International network for ALS research and care (INARC).

The International Network for Amyotrophic Lateral Sclerosis (ALS) Research and Care (INARC) was founded in 2022. INARC's main goals are to offer a platform dedicated to staff members for ALS clinics and research teams who are not physicians. By nurturing experience and expertise exchanges to improve problem solving skills, the ultimate goal is to increase the standard ALS care and research.

Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.

Background: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy.

Amyotrophic lateral sclerosis: exploring pathophysiology in the context of treatment.

Amyotrophic lateral sclerosis (ALS) is a complex, neurodegenerative disorder in which alterations in structural, physiological, and metabolic parameters act synergistically. Over the last decade there has been a considerable focus on developing drugs to slow the progression of the disease. Despite this, only four disease-modifying therapies are approved in North America.

Efficacy and safety of iscalimab, a novel anti-CD40 monoclonal antibody, in moderate-to-severe myasthenia gravis: A phase 2 randomized study.

Background: Increased morbidity in many patients with myasthenia gravis (MG) on long-term immunosuppression highlights the need for improved treatments. The aim of this study is to investigate the safety and efficacy of iscalimab (CFZ533), a fully human anti-CD40 monoclonal antibody, in patients with moderate-to-severe MG receiving standard-of-care (SoC) therapies.

Methods: In this double-blind, placebo-controlled phase 2 study, symptomatic patients (n = 44) despite SoC were randomized 1:1 to receive intravenous iscalimab (10 mg/kg; n = 22) or placebo (n = 22) every 4 weeks for 6 doses in total.

Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

Importance: Additional therapies for amyotrophic lateral sclerosis (ALS) are urgently needed. Immune-mediated complement activation may be involved in ALS pathogenesis as evidenced by the upregulation of terminal components; thus, complement inhibition could potentially slow progression.

Objective: To evaluate the safety and efficacy of the terminal complement C5 inhibitor ravulizumab in adults with ALS.

Oral Edaravone - Introducing a Flexible Treatment Option for Amyotrophic Lateral Sclerosis.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. While pharmacotherapy options remain limited, the Food and Drug Administration (FDA) approved intravenous (IV) and oral edaravone for the treatment of ALS in 2017 and 2022, respectively. With the addition of oral edaravone, patients with ALS may exclusively use oral medications.

Rare-variant and polygenic analyses of amyotrophic lateral sclerosis in the French-Canadian genome.

Purpose: The genetic etiology of amyotrophic lateral sclerosis (ALS) includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both.

SF2Former: Amyotrophic lateral sclerosis identification from multi-center MRI data using spatial and frequency fusion transformer.

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by motor neuron degeneration. Significant research has begun to establish brain magnetic resonance imaging (MRI) as a potential biomarker to diagnose and monitor the state of the disease. Deep learning has emerged as a prominent class of machine learning algorithms in computer vision and has shown successful applications in various medical image analysis tasks.

Speech timing and monosyllabic diadochokinesis measures in the assessment of amyotrophic lateral sclerosis in Canadian French.

Purpose: The primary objective of this study was to determine if speech and pause measures obtained using a passage reading task and timing measures from a monosyllabic diadochokinesis (DDK) task differ across speakers of Canadian French diagnosed with amyotrophic lateral sclerosis (ALS) presenting with and without bulbar symptoms, and healthy controls. The secondary objective was to determine if these measures can reflect the severity of bulbar symptoms.

Method: A total of 29 Canadian French speakers with ALS (classified as bulbar symptomatic [ = 14] or pre-symptomatic [ = 15]) and 17 age-matched healthy controls completed a passage reading task and a monosyllabic DDK task (/pa/ and /ta/), for up to three follow-up visits.

Distinct Plasma Immune Profile in ALS Implicates sTNFR-II in pAMPK/Leptin Homeostasis.

Amyotrophic lateral sclerosis (ALS) is a clinically highly heterogeneous disease with a survival rate ranging from months to decades. Evidence suggests that a systemic deregulation of immune response may play a role and affect disease progression. Here, we measured 62 different immune/metabolic mediators in plasma of sporadic ALS (sALS) patients.

Health utilities and quality-adjusted life years for patients with amyotrophic lateral sclerosis receiving or placebo in FORTITUDE-ALS.

Aims: To estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving versus placebo in FORTITUDE-ALS.

Materials And Methods: We performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated in patients with ALS.