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).

Characterization of LRP4/Agrin Antibodies From a Patient With Myasthenia Gravis.

Background And Objective: To determine whether human anti-LRP4/agrin antibodies are pathogenic in mice and to investigate underpinning pathogenic mechanisms.

Methods: Immunoglobulin (Ig) was purified from a patient with myasthenia gravis (MG) with anti-LRP4/agrin antibodies and transferred to mice. Mice were characterized for body weight, muscle strength, twitch and tetanic force, neuromuscular junction (NMJ) functions including compound muscle action potential (CMAP) and endplate potentials, and NMJ structure.

Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial.

Background: To collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial.

Methods: Twenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT).

Effect of Ezogabine on Cortical and Spinal Motor Neuron Excitability in Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

Importance: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor nervous system. Clinical studies have demonstrated cortical and spinal motor neuron hyperexcitability using transcranial magnetic stimulation and threshold tracking nerve conduction studies, respectively, although metrics of excitability have not been used as pharmacodynamic biomarkers in multi-site clinical trials.

Objective: To ascertain whether ezogabine decreases cortical and spinal motor neuron excitability in ALS.

Minimal manifestation status and prednisone withdrawal in the MGTX trial.

Objective: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).

Methods: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma.

Clinical features of LRP4/agrin-antibody-positive myasthenia gravis: A multicenter study.

Introduction: Our aim in this study was to identify the prevalence and clinical characteristics of LRP4/agrin-antibody-positive double-seronegative myasthenia gravis (DNMG).

Methods: DNMG patients at 16 sites in the United States were tested for LRP4 and agrin antibodies, and the clinical data were collected.

Results: Of 181 DNMG patients, 27 (14.

Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial.

Background: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events.

Methods: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate.

Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies.

Around 20% of patients with myasthenia gravis are acetylcholine receptor antibody negative; muscle-specific tyrosine kinase antibodies (MuSK) were identified as the cause of myasthenia gravis in 30% to 40% of these cases. Anti MuSK myasthenia gravis is associated with specific clinical phenotypes. One is a bulbar form with fewer ocular symptoms.

Induction of Anti-agrin Antibodies Causes Myasthenia Gravis in Mice.

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction (NMJ). Most cases of MG are caused by autoantibodies against the acetylcholine receptor (AChR), muscle-specific kinase (MuSK) and low-density lipoprotein receptor-related protein 4 (LRP4). Recent studies have identified anti-agrin antibodies in MG patients lacking these three antibodies (i.

Screening for lipoprotein receptor-related protein 4-, agrin-, and titin-antibodies and exploring the autoimmune spectrum in myasthenia gravis.

In autoimmune myasthenia gravis (MG), the identification of antibodies and characterization of serological subgroups is of great importance for diagnosis and management of the disease. Our aims were to study the frequency of antibodies against lipoprotein-related protein 4 (LRP4), agrin, and titin using the most recent techniques, and to characterize corresponding clinical features and autoimmune diseases (AID) in 100 MG-patients. The antibody frequencies in the 55 AChR-antibody positive patients were 7% LRP4, 5% agrin, 53% titin, and in the 45 AChR-antibody negative patients 2% MuSK, 2% LRP4, 2% agrin, and 27% titin.

Agrin and low-density lipoprotein-related receptor protein 4 antibodies in amyotrophic lateral sclerosis patients.

Introduction: The prevalence and characteristics of agrin and low-density lipoprotein-related receptor protein 4 (LRP4) antibody-positive amyotrophic lateral sclerosis (ALS) patients were studied.

Methods: We tested 82 ALS patients and 59 controls for agrin and LRP4 antibodies using enzyme-linked immunoassay (ELISA).

Results: We found that 13.

Anti-Sulfoglucuronosyl Paragloboside Antibody: A Potential Serologic Marker of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS.

Randomized Trial of Thymectomy in Myasthenia Gravis.

Background: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone.

Methods: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone.

A new approach to ELISA-based anti-glycolipid antibody evaluation of highly adhesive serum samples.

The enzyme-linked immunosorbent assay (ELISA) is a standard immunoassay used in measuring antibody reactivity (expressed as titers) for glycosphingolipids (GSLs) such as gangliosides and sulfoglycolipids in the sera of patients with Guillain-Barré syndrome (GBS), variants of GBS, and chronic inflammatory demyelinating polyneuropathy (CIDP). In the present study, anti-GSL antibodies were evaluated using a new formula of affinity parametric complex (APC), calculated from limiting-dilution serum assay data, followed by affinity parametric complex criterion (APCC). Using assay results based on APCC, we analyzed serum samples categorized into acute inflammatory demyelinating polyneuropathy (AIDP), acute motor-sensory axonal neuropathy (AMSAN), CIDP, CIDP with myasthenia gravis (MG), and amyotrophic lateral sclerosis (ALS).

Skeletal muscle oxidative capacity in amyotrophic lateral sclerosis.

Introduction: Mitochondrial dysfunction in the motor neuron has been suspected in amyotrophic lateral sclerosis (ALS). If mitochondrial abnormalities are also found in skeletal muscle, assessing skeletal muscle could serve as an important biomarker of disease progression.

Methods: Using 31P magnetic resonance (31P-MRS) and near infrared (NIRS) spectroscopy, we compared the absolute values and reproducibility of skeletal muscle oxidative capacity in people with ALS (n = 6) and healthy adults (young, n = 7 and age-matched, n = 4).

Frequency of radiculopathies in motor vehicle accidents.

This retrospective study compared the frequency of electrodiagnostically confirmed cervical and lumbar radiculopathies in a motor vehicle accident (MVA) population to that of a non-MVA population in 24,651 consecutive initial electrodiagnostic reports. The frequency of cervical radiculopathy was slightly but significantly increased in 8% of the MVA compared to 6% of the non-MVA patients. The frequency of plexopathy was significantly increased in the MVA (3%) compared to the non-MVA patients (2%).

Molecular mimicry: sensitization of Lewis rats with Campylobacter jejuni lipopolysaccharides induces formation of antibody toward GD3 ganglioside.

Recently we have reported cases of demyelinating inflammatory neuropathy showing elevated titers of anti-GD3 antibodies, which occurs rarely in Guillain-Barré syndrome. To examine the correlation between the anti-GD3 antibody titer and Campylobacter jejuni infection, we sensitized female Lewis rats with lipopolysaccharides (LPSs) from serotype HS19 of C. jejuni and examined changes in nerve conduction velocity and nerve conduction block (P/D ratio).

AIDP and CIDP having specific antibodies to the carbohydrate epitope (-NeuAcalpha2-8NeuAcalpha2-3Galbeta1-4Glc-) of gangliosides.

Anti-ganglioside antibodies were investigated in plasma exchange solutions (PEs) from two patients with acute and chronic inflammatory demyelinating neuropathies (AIDP and CIDP). Both cases show markedly elevated antibody titers against the lacto-series gangliosides, GM3, GD3, and GT3. In the CIDP patient, the IgG antibody titer to GD3 was remarkably elevated (titer, 1:10,000), indicating maximal avidity to the tetrasaccharide epitope (-NeuAcalpha2-8NeuAcalpha2-3Galbeta1-4Glc-).