Nemaline Myopathy

Researchers are evaluating the effects of whole-body electrical muscle stimulation (WB-EMS) exercise on neuromuscular and physical function in adults with neuromuscular diseases (NMD) such as amyotrophic lateral sclerosis, spinal muscular atrophy, and myasthenia gravis. People with NMD often face challenges with traditional exercise because of impaired voluntary muscle activation, which can lead to inactivity and worsening health. WB-EMS bypasses these limits by directly stimulating muscle contractions using electrical currents, potentially offering a new way to exercise safely. The intervention uses the Katalyst system, an FDA-cleared device applied off-label, which delivers electrical stimulation to major muscle groups during guided movements. Participants wear a special suit with electrodes connected to an impulse pack controlled via an iPad app. They complete 20-minute supervised exercise sessions 1-2 times per week for 4-8 weeks, following Level 1 strength training videos. Each exercise involves repetitions with stimulation on and off periods, and stimulation levels are adjusted based on participant responses and comfort. Participants will be monitored carefully throughout the study, with evaluations before and after the intervention including neural excitability (using transcranial magnetic stimulation), motor unit behavior (via electromyography and nerve conduction studies), and functional tests like walking, balance, and strength assessments. Patient-reported outcomes on fatigue, pain, and quality of life will also be collected. Safety monitoring is strict, and the study will provide preliminary data on the feasibility and impact of WB-EMS exercise for adults with NMD.

Researchers are studying congenital myopathies, a group of neuromuscular diseases present from birth, including central core disease, centronuclear/myotubular myopathy, congenital fiber type disproportion, multiminicore disease, nemaline myopathy, rigid spine muscular dystrophy, SELENON (SEPN1) myopathy, RYR1 myopathy, ADSS1 (ADSSL) myopathy, and other undefined congenital myopathies. The goal is to better understand the genes and proteins involved in muscle function and disease to improve diagnosis and treatment in the future. The study involves identifying and describing new genes and proteins related to skeletal muscles and detecting genetic changes that cause neuromuscular diseases. Researchers study how these mutations are inherited in families and how they lead to muscle weakness. Participants with congenital myopathies provide medical records, blood or saliva samples, and muscle tissue samples if available. Family members are also invited to donate blood samples to help understand disease inheritance. Participants contribute medical records and biological samples for genetic and muscle tissue studies. The research team examines gene expression and protein levels to correlate with clinical symptoms. The main outcome is identifying genes responsible for neuromuscular diseases, a process that can take from several days to decades. The study welcomes participants worldwide, does not require travel to Boston, and participation is free of charge.

This research aims to understand the progression and clinical features of nemaline myopathies by establishing a detailed patient group in Spain. It looks to identify the specific genes and mutations involved, explore the relationship between symptoms and genetics, and describe how the disease develops without treatments that change its course. The study also seeks to find reliable markers and measurements for future clinical trials and align Spanish research with international efforts. Participants will undergo various assessments, including muscle ultrasound to evaluate muscle condition, motor function tests using several standard scales, and complete physical exams focusing on muscle strength and joint measurements. Additional evaluations include respiratory, cardiac, nutritional, and quality of life assessments, as well as video recordings to analyze movement in detail. These tests will be collected both retrospectively and prospectively over an average of five years. During the study, participants will be regularly monitored through clinical data collection, functional tests, and respiratory evaluations to observe changes over time. Researchers will track muscle condition by ultrasound and assess motor function using tools like CHOP-INTEND and the Motor Function Measure. The study will also observe respiratory function, nutritional status, and quality of life changes. This long-term follow-up aims to provide comprehensive information about the natural course of nemaline myopathies.

Researchers are studying the natural history and genetic basis of inherited neurological disorders, including hereditary peripheral neuropathies, myopathies, muscular dystrophies, motor neuron disorders, mitochondrial myopathies, neurocognitive disorders, and others. This observational study aims to better understand these rare and complex diseases by examining symptoms, disease progression, treatment effects, and psychological and behavioral impacts across a broad range of inherited neurological conditions. Participants include children and adults with diagnosed or suspected inherited neurological diseases, as well as their unaffected relatives. They will undergo detailed medical and family history reviews, physical and neurological exams, and may have blood, urine, or genetic testing, along with brain wave recordings and psychological evaluations. Imaging tests and muscle or nerve testing may also be performed based on individual symptoms. Samples such as blood or skin biopsies may be collected for genetic analysis. Throughout the study, participants will be evaluated with various assessments including neurological exams, psychological tests, and possibly imaging scans. Researchers will track genetic disease identification and deep phenotyping of rare neurological disorders. The study aims to collect data over a long duration to enhance understanding, diagnosis, and future research. Participants may also contribute samples for laboratory studies, and the study supports training of fellows and students. The total enrollment is planned for up to 3,500 participants and their relatives, with ongoing follow-up until genetic diagnoses are made.

This research aims to understand the natural history and muscle fatigability in patients with three rare congenital myopathies: Central Core Disease/Multi-Minicore Disease (CCD/MmD), Nemaline Myopathy (NEM), and Centronuclear Myopathy (CNM). These conditions cause muscle weakness in the arms, legs, and other muscles such as those for breathing, facial movement, and swallowing. Since no curative treatments exist, the study seeks to gather detailed information about disease progression and identify sensitive clinical measures and biomarkers over 24 months to prepare for future clinical trials. The study has two parts. The first is a 2-year prospective cohort study involving 45 patients who will have five visits every six months to monitor disease progression. The second is a cross-sectional observational study focusing on muscle fatigability that will include 75 patients with two visits for assessments. Tests will include muscle strength and endurance measures, imaging (MRI and ultrasound), walking ability, quality of life questionnaires, and evaluations of muscle fatigability and fatigue sensation. Some patients may participate in both parts. Participants will undergo comprehensive evaluations, including motor function measures at multiple time points, endurance tests, muscle imaging, and questionnaires assessing fatigue and quality of life. Other assessments include pulmonary function tests, muscle strength testing, and blood tests for biomarkers like creatine kinase and vitamin D3. The study involves traveling to study sites in Nijmegen and Utrecht for testing. Researchers will closely monitor changes in motor function, muscle fatigability, and other outcomes to better understand these myopathies and support future treatment trials.

Researchers are conducting the WiTNNess study to document the natural course and variations of muscle disease caused by changes in the TNNT1 gene. This observational study focuses on autosomal recessive TNNT1-associated muscle disease, including infantile-onset and childhood-onset nemaline rod myopathy. The study aims to identify meaningful outcome measures for future clinical trials evaluating new disease-modifying therapies. WiTNNess welcomes children and adults worldwide to participate. The study has two groups: a prospective cohort and a cross-sectional cohort. The prospective group enrolls participants shortly after diagnosis during early infancy and follows them over time with repeated assessments until they reach the primary study outcome. The cross-sectional group includes participants who join at any time after diagnosis and contribute data during a single assessment. Assessments may occur at home, the Clinic for Special Children, or partnering sites, depending on participant needs. Participants undergo various assessments such as vital signs, physical exams, growth measurements, motor milestone documentation, and blood tests. Some may have non-invasive heart ultrasound and chest X-rays. Those in the prospective cohort have ongoing follow-up, while cross-sectional participants provide information once. The primary outcome measured is event-free survival over up to 15 years, with secondary outcomes including motor milestones and thriving. The study involves close monitoring to understand disease progression under current treatments.