Nemaline Myopathy

This is a prospective, longitudinal, observational study designed to characterize the natural history of Nemaline Myopathy (NM), a rare congenital neuromuscular disorder. The study will follow up to 10 participants of any age with genetically confirmed NM over a period of three years. Data will be collected during routine annual hospital visits and include clinical, motor, respiratory, and quality-of-life assessments. The goal is to improve clinical trial readiness by identifying disease-specific outcome measures and potential biomarkers.

In the Congenital Myopathy Research Program at Boston Children's Hospital and Harvard Medical School, the researchers are studying the congenital myopathies (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), RYR1 myopathy, ADSS1 (ADSSL) Myopathy and undefined congenital myopathies. The primary goal of the research is to better understand the genes and proteins (gene products) involved in muscle functioning and disease. The researchers hope that our studies will allow for improved diagnosis and treatment of individuals with congenital myopathies in the future. For more information, visit the Laboratory Website at www.childrenshospital.org/research/beggs

The objective of this natural history study is to comprehensively characterize the disease progression and clinical features of nemaline myopathies. The study aims to establish a well-defined cohort of patients in Spain, enabling long-term follow-up and facilitating recruitment for future clinical trials.

This single-arm pilot study evaluates the effects of whole-body electrical muscle stimulation (WB-EMS) exercise on neuromuscular and physical function in adults with neuromuscular disease (NMD). Due to motor unit impairments, NMD patients often cannot tolerate traditional exercise. WB-EMS bypasses voluntary activation limits by directly stimulating muscle contractions. Up to 50 adults with conditions like ALS, SMA, and MG will undergo 20-minute supervised WB-EMS sessions (1-2 times weekly for 4-8 weeks) using the Katalyst system. Outcomes include neural excitability (TMS), motor unit behavior (EMG, NCS), functional tests (walk, balance, strength), and patient-reported fatigue, pain, and quality of life. Strict safety monitoring and exclusion criteria are in place. This study will provide preliminary data on WB-EMS as a potential exercise modality for NMD.

The skeletal muscle ryanodine receptor (RYR1) gene encodes an important calcium channel in skeletal muscle, with an important role in muscle contraction. Mutations (i.e. disease-causing changes) in RYR1 are associated with an immensely wide range of clinical problems, ranging from inborn muscle conditions with profound weakness at birth ("congenital myopathies"), to a potentially fatal anaesthesia complication ("Malignant Hyperthermia, MH") in otherwise healthy individuals. Although RYR1-related conditions are believed to be amongst the most common neuromuscular disorders, their precise prevalence (i.e. the number of cases in a particular population at a given time) is currently unknown. Moreover, there is no information regarding the relative frequency of specific congenital myopathies, MH and related manifestations, such as the associated bleeding abnormality recently described by our team. The lack of reliable prevalence data represents a major obstacle to addressing the needs of individuals affected by RYR1-related conditions, to appropriate resource allocation, and to preparation for clinical studies ("trial-readiness") essential for therapy development. To address this shortcoming, we will conduct an international collaborative study involving neuromuscular and MH centres from the UK and the Netherlands, focusing on the prevalence of RYR1-related conditions, as a group and per subtype. The countries participating in this study were included because of 1) centralized RYR1 testing, 2) the presence of at least one database/registry with population-wide coverage capturing RYR1-related disorders and 3) of national myopathy and MH expertise centres. Information regarding RYR1-mutated individuals and their specific diagnosis will be obtained from national databases/registries, and analysed utilizing statistical methods that are well-established in the field of epidemiology. This study will provide important information regarding the actual disease burden of RYR1-related disorders on a wider scale, inform appropriate research resource allocation, and preparation for trial readiness. This study will be funded by the RYR1-Foundation.

The goal of this study is to establish a research network to help define the natural disease history and clinical outcome measures for Nemaline Myopathy (NM).

Core myopathies (CCD/MmD), nemaline myopathies (NEM) and centronuclear myopathies (CNM) are three types of rare congenital myopathies. Not much is known about the natural history and no curative treatment is available for these groups. Also patients report fatigability as one of their symptoms. The goal of this observational study is to study the natural history during 24 months to achieve trial readiness and to study the muscle fatigability in CCD/MmD, NEM and CNM.