Limb-Girdle 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 studying the safety and effectiveness of a single dose of nexiguran ziclumeran (NTLA-2001) compared to a placebo in people with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This phase 3, multinational, randomized, double-blind, placebo-controlled trial involves about 60 participants with this nerve disease and genetic condition affecting the peripheral nervous system. Participants will be randomly assigned to receive a single intravenous infusion of either nexiguran ziclumeran 55 mg or a placebo of normal saline. To give everyone a chance to receive the study drug, participants may switch to the other treatment group at either 12 or 18 months, depending on specific study criteria. The study is designed to compare the effects of the drug and placebo over time. During the study, participants will be monitored for nerve function using the Modified Neuropathy Impairment Score +7 (mNIS+7) over 18 months and blood levels of serum transthyretin at 29 days and 18 months. Quality of life, body mass index, and other health measures will also be evaluated. The study includes careful safety monitoring and will last up to 18 months with ongoing assessments to track participants' nerve health and overall well-being.

Researchers are conducting a multicenter, prospective observational study to understand the natural history of Charcot-Marie-Tooth Disease, Type 4J (CMT4J), a rare neurodegenerative and neuromuscular condition confirmed by specific genetic testing. The study will enroll 20 participants of any age who have a molecularly confirmed diagnosis of CMT4J. The purpose is to collect detailed health information and disease progression data over time, without providing any investigational treatments. Participants will follow a uniform protocol with visits scheduled every 12 months plus a 4-week window, for up to 2 years. At each visit, researchers will collect demographic and medical history data, perform physical and neurological exams, standard lab tests, and use several disease outcome measures. Additional assessments may include neuropsychological tests, nerve conduction studies, muscle MRI, pulmonary function tests, and scoliosis x-rays. Early termination visits are planned if participants leave before completing the study. Throughout the study, participants will undergo thorough evaluations to monitor their condition and collect data relevant to CMT4J progression. This includes clinical exams, imaging, lab tests, and questionnaires. Researchers will use this information to study disease patterns and outcomes over the 2-year follow-up period. No investigational products are administered, and visits may be unscheduled if necessary with approval. Participants are expected to comply with study procedures and travel requirements.

This clinical trial is focused on people diagnosed with Facioscapulohumeral Muscular Dystrophy (FSHD), specifically types FSHD1 or FSHD2. The study aims to evaluate the safety and effectiveness of an intravenous drug called del-brax (also known as AOC 1020) compared to a placebo. This is a randomized, double-blind, placebo-controlled Phase 3 trial sponsored by Avidity Biosciences, Inc. It seeks to better understand how del-brax affects muscle strength and disease progression in FSHD patients. Participants will be randomly assigned to receive either del-brax or a placebo through intravenous infusions every six weeks for a total of 13 doses over a 72-week treatment period. After the last dose at Week 72, a final assessment will take place at Week 78. Those who finish the treatment phase may have the option to join an open-label extension study if approved. Participants who do not join the extension will be monitored for safety for an additional 12 weeks. An independent committee will regularly review safety and effectiveness data throughout the study. During the trial, participants will visit the clinical site regularly for infusions and assessments. Researchers will measure muscle strength using the Quantitative Muscle Testing (QMT) composite score, along with other tests such as walking speed, timed mobility, patient-reported physical function, pain levels, and biomarkers related to FSHD. The total study duration is approximately 78 weeks, including screening, treatment, and follow-up periods. Safety and tolerability will be closely monitored throughout and after the treatment phase.

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.

This research is focused on patients with slowly progressive neuromuscular diseases who experience breathing difficulties requiring support from non-invasive ventilation (NIV). The study aims to assess the safety and effectiveness of a new type of NIV called volume-targeted ventilation (VT-NIV), which adjusts the pressure delivered to the lungs to reach a specific breath volume. This approach is being evaluated to better control carbon dioxide levels, which are linked to clinical outcomes in these patients. Participants currently using fixed bi-level NIV will undergo a two-night hospital stay for assessment. On the first night, their carbon dioxide control will be measured using their usual ventilator. On the second night, they will switch to VT-NIV. After discharge, participants will use VT-NIV at home for three months. The study will observe both patients with well-controlled and poorly controlled carbon dioxide to evaluate safety and potential benefits of VT-NIV. During the study, researchers will collect data from the ventilation devices and patient questionnaires to assess adherence and quality of life. Measurements include overnight transcutaneous carbon dioxide levels, oxygen desaturation, sleep comfort, and health-related quality of life. The follow-up visit at three months will review these outcomes and monitor participant safety. The total participation includes the initial two-night hospital stay and the three-month home use period.

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic condition that causes ongoing weakening of skeletal muscles. This research investigates a patient-driven health platform and registry called BetterLife FSHD, designed to support people living with FSHD by connecting them to personalized resources, tools, and relevant research opportunities. The platform also collects secure health and experience data to better understand the disease and improve care and treatments. Participants in BetterLife FSHD complete a series of short surveys at quarterly and yearly intervals. These surveys cover topics like demographics, health history, diagnosis and progression of FSHD, management strategies, and quality of life factors such as pain, fatigue, and mental health. Based on their responses, participants receive personalized resources and are informed about clinical trials and research studies they may qualify for. The collected data is securely stored and shared in a de-identified form with approved researchers and organizations. Throughout the study, participants provide health information regularly through surveys over a period of up to 10 years. The research team assesses longitudinal health data annually and tracks self-reported FSHD progression every six months. Additional patient-reported outcomes related to anxiety, depression, pain, sleep, fatigue, mobility, physical activity, falls, and other health aspects are collected quarterly or yearly. This ongoing data collection supports a comprehensive understanding of living with FSHD and advances research efforts.

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.