Clinical Research Directory

Detecting Fatigue From Voice in Generalised Myasthenia Gravis

The goal of this observational study is to learn if computer analysis of voice recordings can detect a type of exhaustion called "central fatigue" in adults with generalised myasthenia gravis. The main questions it aims to answer are: 1. Can advanced voice analysis accurately tell when participants are experiencing deep exhaustion based on how they speak? 2. How easy and acceptable is voice-based fatigue monitoring for people with myasthenia gravis? Participants will: 1. Record themselves reading short passages and answering questions out loud twice daily (morning and evening), twice a week, for 4 weeks. 2. Answer brief questionnaires about their energy levels, mood, and myasthenia gravis symptoms during each session. 3. Use their own devices (computer, tablet, or smartphone) to complete all study activities online from home.

Proteomic Changes in Patients With Myasthenia Gravis and Ravulizumab

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder primarily caused by antibodies targeting postsynaptic components of the neuromuscular junction, most commonly the acetylcholine receptor (AChR). In AChR-positive generalized MG, IgG1 and IgG3 antibodies activate the classical complement pathway, leading to membrane attack complex-mediated damage of the postsynaptic membrane and impaired neuromuscular transmission. Complement inhibition has therefore emerged as an effective therapeutic strategy. Ravulizumab, a long-acting monoclonal antibody targeting complement component C5, has demonstrated clinical efficacy in reducing disease severity in patients with AChR-positive generalized MG. However, clinical responses to complement inhibition remain heterogeneous, and reliable biomarkers to monitor treatment response and neuromuscular junction recovery are currently lacking. Blood-based proteomics represents a powerful approach for identifying molecular changes associated with disease activity and treatment response. In particular, aptamer-based proteomic platforms such as the SomaScan® assay allow high-throughput, highly sensitive quantification of thousands of circulating proteins from small volumes of plasma or serum. The primary aim of this study is to identify proteomic changes in patients with generalized MG treated with Ravulizumab, with a specific focus on proteins involved in neuromuscular junction regeneration and repair. By leveraging advanced proteomic technologies in a real-world clinical setting, this study seeks to identify biomarkers that may help monitor treatment response, guide optimization of concomitant immunosuppressive therapies, and improve patient stratification. Ultimately, the identification of molecular pathways associated with neuromuscular junction regeneration may open new therapeutic perspectives for autoimmune neuromuscular disorders.

Meningococcal Vaccination in Patients on Complement Inhibitors

Myasthenia gravis is an autoimmune neurological disorder caused by autoantibodies directed predominantly against components of the postsynaptic membrane of the neuromuscular junction. Anti-aquaporin-4 antibody-associated neuromyelitis optica (AQP4-IgG) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by three main clinical manifestations: transverse myelitis, optic neuritis, and postrema area syndrome. Over the past five years, the FDA and EMA have approved complement inhibitor drugs for the treatment of generalized myasthenia gravis with anti-AChR antibody positivity and for neuromyelitis optica spectrum disorders with anti-AQP4 antibody positivity. Eculizumab is a humanized monoclonal antibody that binds to the C5 fragment of the human complement specifically and with high affinity, inhibiting its cleavage in C5a and C5b and preventing the formation of the membrane attachment C5b-9 complex (MAC) of the terminal portion of the complement cascade. This monoclonal antibody maintains the early components of complement activation (C3b), which are essential for the opsonization of microorganisms and the clearance of immune complexes. Ravulizumab is a monoclonal antibody derived from eculizumab, through the substitution of four specific amino acids, which binds specifically to complement protein C5. These substitutions increase the dissociation of the monoclonal antibody from the C5 fragment within the endosome and promote the recycling of the neonatal Fc receptor-mediated unbound antibody, extending its half-life and duration of action up to an interval of 8 weeks. Zilucoplan is a synthetic macrocyclic peptide composed of 15 amino acids that specifically binds the complement protein C5, inhibiting its cleavage into C5a and C5b by C5 convertase, which results in an underregulation of MAC assembly and cytolytic activity. In addition, this drug binds the C5b fraction of C5, creating a steric encumbrance for the binding of C5b to C6 and preventing subsequent assembly of the MAC if any C5b is formed. Due to their mechanism of action, eculizumab, ravulizumab and zilucoplan result in an increased susceptibility of the patient to systemic infections by encapsulated bacteria (S. pneumoniae, H. influenzae, N. meningitidis). To reduce the risk of infection, all patients should be vaccinated against serogroups A, B, C, W, Y at least 2 weeks prior to treatment; patients who start treatment before 2 weeks after administration of meningococcal vaccines should be given appropriate antibiotic prophylaxis for up to 2 weeks after vaccination. Currently, there is no global agreement on the vaccination schedule to be followed after the first dose. According to Italian guidelines, a booster dose is recommended for the monovalent vaccine only at least 1 month after the first administration and a period of antibiotic prophylaxis beyond the first two weeks after the first doses is not indicated. The primary objective of the study is to evaluate the antibody titles after tetravalent meningococcal vaccination (serogroups A, C, W, Y) in patients candidate to complement inhibitors therapy.

Myasthenia Gravis Foundation of America Global MG Patient Registry

The goal of this observational study is to learn about the experiences of people living with Myasthenia Gravis (MG) in the United States. The main questions it aims to answer are: * How and when are people with MG diagnosed? * What are the most common symptoms associated with MG? * What treatments are being used to treat MG? * What are the impacts of MG on activities of daily living, employment and quality of life? * What are the experiences with exacerbation, hospitalization and healthcare access for people with MG? Participants will answer a survey to enroll in the study, and be invited to fill out an update survey twice a year.