Emery-Dreifuss Muscular Dystrophy

Researchers are evaluating anitocabtagene autoleucel (anito-cel), a BCMA-directed CAR-T cell therapy, in adults with generalized myasthenia gravis (GMG) classified as MGFA Grade 2 to 4a. This Phase 1 open-label, multi-center study aims to assess the safety, tolerability, and preliminary efficacy of anito-cel in patients who require immunosuppressive therapy as determined by their neurologist. The study focuses on identifying dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), and selecting the recommended Phase 2 dose (RP2D) for treatment. The study includes sequential phases: screening, enrollment with leukapheresis to collect cells, pretreatment with a standard lymphodepletion chemotherapy regimen for 5 days, and a single intravenous infusion of anito-cel cells. Optional bridging therapy may be given while the CAR-T cells are prepared. Following infusion, participants will be closely monitored for safety and efficacy outcomes over time. Participants will undergo safety monitoring for at least 28 days after infusion, with safety data collected throughout the study duration of up to 24 months. Clinical effects will be evaluated using measures including the Myasthenia Gravis Activities of Daily Living (MG ADL) score, Quantitative Myasthenia Gravis (QMG) score, and Myasthenia Gravis Composite (MGC) scale. Additionally, blood tests will monitor autoantibody levels and pharmacokinetics of the therapy. This comprehensive follow-up ensures careful assessment of treatment impact and participant health.

Researchers are evaluating the safety and tolerability of a single intravenous infusion of AB-1003 gene therapy in adults diagnosed with limb girdle muscular dystrophy type 2I/R9 (LGMD2I/R9). This study includes sequential dose-level groups to carefully assess the effects of the treatment. The trial is a two-part, multicenter study with randomized, double-blind, placebo-controlled design to ensure reliable results for adults aged 18 to 65 with confirmed FKRP gene mutations linked to LGMD2I/R9. Participants receive a single intravenous infusion of AB-1003 at one of two dose levels or a placebo in the first part of the study. This dose-escalation phase helps to monitor safety and tolerability before moving to the next phase. The treatment is given as one infusion only, and participants are monitored closely for any side effects or adverse events throughout the study period. During the study, participants will undergo regular evaluations including monitoring for adverse events for up to 52 weeks. Assessments include clinical exams, laboratory tests, and imaging to track the participants’ health and response to the infusion. Safety monitoring is a key focus, with detailed attention to heart function and liver and kidney health. Participants are expected to comply with study procedures and contraception use as required, with the overall study duration spanning approximately one year.

Researchers are evaluating whether amino acid supplementation combined with a structured diet and exercise program can improve body composition and physical performance in adults with facioscapulohumeral muscular dystrophy (FSHD). This rare muscle disease causes progressive weakness mainly in the face, shoulders, and upper body, leading to reduced strength, aerobic capacity, walking ability, and increased fatigue. The study also compares responses between people with FSHD and healthy individuals matched by age and sex. Participants with FSHD will undergo two 6-month treatment phases with a 3-month break in between, receiving either amino acid supplements or placebo in random order. Healthy volunteers will complete one 6-month phase receiving exercise and diet only. All participants follow a personalized diet and home-based exercise plan including aerobic and resistance training. The amino acid supplement is given twice daily under blinded conditions. Throughout the 15-month study period, researchers will assess body composition, muscle strength, aerobic fitness, walking performance, and daily physical activity using tools like handgrip strength tests, gait analysis, VO2 max measurement, and accelerometers. Safety is monitored mainly for minor injuries related to exercise. The study aims to measure changes in fat mass, lean mass, aerobic capacity, muscle strength, and walking ability from start to end of treatment.

Researchers are evaluating markerless gait analysis in adults with neuromuscular diseases or in asymptomatic volunteers. This study aims to improve monitoring of walking biomechanics, which current gait tests may not fully capture, especially given the slow progression of symptoms in these conditions. The study focuses on quantifying gait parameters using a portable digital device to allow for easier and effective assessment without complex equipment. Participants will walk with shoes in a gait analysis room while wearing VICON markers on their body. Simultaneously, two smartphones will record video to compare the traditional marker-based gait analysis with the markerless system using motion analysis software. All participants receive the same intervention involving walking and simultaneous recording for comparison. During the study, participants will be evaluated on how well the markerless system correlates with the VICON system on the first day. Researchers will collect data on walking biomechanics through the two methods. Participants must be able to walk and stand independently for certain periods and will be monitored for their ability to perform specific physical tasks. The study includes adults aged 18 to 65, both with neuromuscular diseases of genetic origin and without symptoms, with total participation lasting at least the assessment day.

Researchers are investigating how customizing the stiffness of ankle-foot orthoses (AFOs) separately for upward and downward foot movements affects walking in people with neuromuscular disorders causing weakness in the lower leg muscles. This pilot study compares a new spring-hinged AFO with adjustable stiffness in both directions to three types of standard spring-like AFOs that have the same stiffness in both directions. The goal is to understand how these devices influence walking biomechanics, energy use, speed, and balance. Participants will receive a custom-made spring-hinged AFO featuring the NEURO SWING4 system ankle joint. The stiffness will be optimized individually using a special algorithm based on six different stiffness configurations tested after delivery. Participants will then use this optimized AFO at home for six weeks. At baseline, they will also be tested with three prefabricated spring-like AFOs of varying stiffness and their own AFO if they have one, as well as walking with shoes only. During the study, researchers will assess walking using 3D gait analysis to measure ankle and knee angles and velocities, along with walking energy cost, speed, standing balance, and participants' perceptions of physical function and walking ability. Measurements will be taken immediately after fitting the optimized AFO and again after six weeks of use. This comprehensive evaluation aims to clarify how individualized AFO stiffness affects mobility and daily functioning in people with lower leg muscle weakness.

Researchers are evaluating the BrainGate2 Neural Interface System to understand its safety and feasibility for people with tetraplegia, including those with severe speech impairments. The study aims to develop a medical device that could help individuals with paralysis regain abilities that normally depend on hand movement or speech. The project focuses on people with conditions such as spinal cord injury, brainstem stroke, muscular dystrophy, amyotrophic lateral sclerosis, and other motor neuron disorders. The intervention involves placing up to six small BrainGate2 sensors into the motor-related cortex of the brain, including areas related to speech. These sensors connect to percutaneous pedestals to record neural signals, which are monitored weekly for a year or longer. The study is designed to collect preliminary safety data and demonstrate the ability of participants to control computer cursors and other assistive devices using their thoughts. Participants will be involved in regular neural recordings and evaluations to track the device's safety and functionality over a one-year post-implant period. Researchers will assess the feasibility of the system and gather data to inform larger future studies, including neural decoding methods and success measures. The total participation duration may extend beyond one year, with ongoing monitoring of device performance and participant ability to control assistive technologies.

Researchers are studying dystroglycanopathies, a group of muscular dystrophies caused by abnormal glycosylation of alpha-dystroglycan. These inherited disorders involve mutations in more than 20 known genes and cause progressive muscle weakness ranging from congenital muscular dystrophy affecting the brain and eyes to adult-onset limb girdle muscular dystrophy. The study aims to describe early signs and symptoms and collect information needed for future clinical trials. This observational study includes clinical evaluations at the University of Iowa, where participants undergo muscle strength and motor ability testing, lung function tests, quality of life and activity assessments, and a review of their medical history. These evaluations will be repeated approximately once a year. Financial assistance is available to help with travel, and genetic testing support is offered to those diagnosed through muscle or skin biopsy analysis. Participants will be involved in regular assessments to monitor muscle function, including a 10-meter walk test and a 4-stair climb test, repeated annually through the study. Researchers will use this information to improve healthcare recommendations and establish a baseline for future studies and potential treatments. The study allows participation of individuals of any age and sex with varying degrees of muscle weakness but who are otherwise in relatively good health.

Researchers are conducting a 10-year observational study called the Congenital Muscle Disease Patient and Proxy Reported Outcome Study (CMDPROS). This study aims to collect and analyze care data and adverse events for various congenital muscle diseases using the Congenital Muscle Disease International Registry (CMDIR). The study focuses on individuals with diagnoses such as congenital muscular dystrophy, congenital myopathy, congenital myasthenic syndrome, and related conditions, including those without genetic confirmation. Understanding these conditions better will help improve care standards and support future clinical trials. Participants register in the CMDIR by providing demographic information and completing an intake survey. They are also asked to share medical records related to their diagnosis and treatment, such as genetic testing results, muscle biopsy reports, pulmonary function tests, sleep studies, clinic notes, and hospital discharge summaries. The study collects data on multiple disease subtypes and tracks various health events and care parameters over time, aiming to build a comprehensive database. Throughout the study, participants provide ongoing information about their health status and adverse events, which researchers verify using medical records. Key outcomes include survival rates, hospitalization frequency, respiratory complications, and other health complaints. The study will also analyze measures like ejection fraction, lung function, sleep study results, growth, fractures, and bone density. Data collected will contribute to evidence-based care guidelines and help identify meaningful outcomes for future clinical trials. Participation requires no travel as data collection is done remotely through the registry.

Researchers are exploring the use of electrocorticography (ECoG) signals to control complex devices for motor and speech functions in adults who have severe neurological disorders such as ALS, spinal cord injury, stroke, multiple sclerosis, and muscular dystrophies. This study aims to determine if brain signals recorded directly from the brain's surface can be used to operate robotic systems and generate speech, providing new communication and neuroprosthetic options for affected individuals. Participants will use a high-performance ECoG-based neural interface involving subdural cortical electrodes combined with the Blackrock NeuroPort Array device. The study involves training and assessing participants' ability to control a robotic system and produce speech via brain signals. The intervention is device-based, and follow-up includes a long-term monitoring period of up to 6 years after implantation to track safety and functional outcomes. During the study, participants will undergo neurological assessments and training with the ECoG device. Researchers will monitor safety by tracking treatment-emergent adverse events and evaluate the primary and secondary objectives related to motor and speech control capabilities. The study includes regular follow-up visits over several years to assess device performance, participant function, and tolerability of the implant. Total participation may last up to 6 years post-implantation for ongoing safety and efficacy evaluation.

Researchers are evaluating the efficacy, safety, and tolerability of zeleciment rostudirsen (DYNE-251), given intravenously every 4 weeks, in ambulatory male children and adolescents aged 4 to 18 years with Duchenne muscular dystrophy (DMD) who have a specific mutation suitable for exon 51 skipping. This Phase 3 study aims to provide important information about this treatment option for this group of patients with DMD. The study includes three distinct periods: a Screening period lasting up to 6 weeks, a Placebo-Controlled Period of 72 weeks where participants are randomly assigned to receive either zeleciment rostudirsen or placebo every 4 weeks, and an open-label Long-Term Extension Period of up to 96 weeks during which all participants receive the study drug every 4 weeks. This design allows researchers to compare the treatment to placebo and then assess longer-term effects. Participants will be closely monitored throughout the study with regular assessments including the primary outcome of Rise From Floor (RFF) velocity measured at baseline and Week 73. Various secondary measures such as walking speed, stair climbing ability, lung function, patient global impressions, blood creatine kinase levels, and safety through adverse event monitoring and blood drug levels will be collected up to Week 169 or study completion. The total study duration including the extension is up to approximately 168 weeks. This thorough evaluation helps understand the treatment’s impact and safety over time.