Respiratory Muscle Involvement Research Articles

Clinical practice guidelines for Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most common X-linked recessive disorder of the neuromuscular system. The incidence of DMD in male newborns is approximately 1 in 3500. It is caused by mutations of dystrophin (DMD) gene in Xp21.2 region. The main clinical manifestations of DMD include progressive and symmetrical myasthenia. Due to the involvement of respiratory muscles and myocardium, DMD patients usually die before the age of 30. Genetic testing can uncover the mutations in 93.1% of the patients and lay a foundation for early treatment, improving the quality of life of patients, and preventing the families from having further affected children. This guideline has combined relevant research, guideline and consensus issued at home and abroad, and summarized genetic knowledge and clinical treatment for DMD, with the aim to standardize the diagnosis, treatment and prevention for patients and their families.

Early respiratory involvement leading to respiratory failure in a case of Systemic sclerosis - Polymyositis overlap

Polymyositis is an autoimmune myopathy with a preponderance to involve proximal limb muscles in a symmetrical manner. Type two respiratory failure and severe bulbar weakness is not a common mode of initial presentation of polymyositis – systemic sclerosis overlap syndrome. We present a case of a middle age female , who presented with dysphagia, nasal regurgitation, aspiration of food and proximal muscle weakness, worsening over 6 months duration. The disease was rapidly progressing and culminated in severe respiratory muscle weakness and respiratory arrest necessitating invasive ventilation. The diagnosis of sero- negative polymyositis and systemic sclerosis overlap syndrome was made and she achieved a remarkable recovery with intensive care and meticulous immunosuppressive therapy. Physicians should be aware of the rapid respiratory muscle involvement in systemic sclerosis and Polymyositis overlap since timely initiation of treatment is life saving.

Riluzole-induced interstitial lung disease is a rare and potentially life-threatening adverse event successfully treated with high-dose steroid therapy: Case reports and review of the literature

Riluzole (RZ)-induced interstitial lung disease (RZ-ILD) is a rare and potentially life-threatening adverse event in amyotrophic lateral sclerosis (ALS) patients, which is rarely reported. Therefore, the optimal treatment for RZ-ILD is unclear. We describe herein three Japanese cases of ALS complicated with RZ-ILD, of which two were successfully treated with high-dose steroid therapy. In our all ALS cases with RZ-ILD, the duration of RZ exposure until RZ-ILD onset was within 2 months. All three cases showed respiratory symptoms, dorsal predominant ground-glass opacities by imaging analysis, and abnormal laboratory findings associated with interstitial lung diseases, such as Krebs von den Lungen-6 and surfactant protein-D. Intravenous high-dose steroid therapy together with the discontinuation of RZ in two cases with respiratory symptoms markedly ameliorated their symptoms and abnormal findings of RZ-ILD. One case showed mild respiratory symptoms compared with the others and recovered after the withdrawal of RZ only. According to previous case reports and our cases, RZ-ILD may develop 2 months after initiating RZ and exacerbate respiratory symptoms rapidly in ALS patients with severe respiratory muscle involvement or complicating aspiration pneumonia. Transient high-dose steroid therapy in addition to discontinuation of RZ might be a good therapeutic option for RZ-ILD.

Characteristics of respiratory muscle involvement in myotonic dystrophy type 1

The pathophysiology of respiratory muscle weakness in myotonic dystrophy type 1 (DM1) remains incompletely understood. 21 adult patients with DM1 (11 men, 42 ± 13 years) and 21 healthy matched controls underwent spirometry, manometry, and diaphragm ultrasound. In addition, surface electromyography of the diaphragm and the obliquus abdominis muscle was performed following cortical and posterior cervical magnetic stimulation (CMS) of the phrenic nerves or magnetic stimulation of the lower thoracic nerve roots. Magnetic stimulation was combined with invasive recording of the twitch transdiaphragmatic and gastric pressure (twPdi and twPgas) in 10 subjects per group. The following parameters were reduced in DM1 patients compared to control subjects: maximum inspiratory pressure (MIP; 40.3 ± 19.2 vs. 95.8 ± 28.5 cmH2O, p < 0.01), diaphragm thickening ratio (DTR; 2.0 ± 0.4 vs. 2.7 ± 0.6, p < 0.01), twPdi following CMS (10.8 ± 8.3 vs. 21.4 ± 10.1 cmH2O, p = 0.03), and amplitude of diaphragm compound muscle action potentials (0.10 ± 0.25 vs. 0.46 ± 0.35 mV; p = 0.04). MIP and DTR were significantly correlated with the muscular impairment rating scale (MIRS) score. Maximum expiratory pressure (MEP) was reduced in DM1 patients compared to controls (41.3 ± 13.4 vs. 133.8 ± 28.0 cmH2O, p < 0.01) and showed negative correlation with the MIRS score. Pgas following a maximum cough was markedly lower in patients than in controls (71.9 ± 43.2 vs. 102.4 ± 35.5 cmH2O) but without statistical significance (p = 0.06). In DM1, respiratory muscle weakness relates to clinical disease severity and involves inspiratory and probably expiratory muscle strength. Axonal phrenic nerve pathology may contribute to diaphragm dysfunction.

Guillain-Barre syndrome

Guillain-Barre syndrome is the most common and most severe acute flaccid paralysis, usually preceded by an infection or immune stimulation. A literature review of the last five years in Pubmed, Scopus, Embase, and Web of Science databases was done. Data were collected from epidemiological studies using the keywords. Guillain-Barre syndrome (GBS) is an acute, severe, and fulminant polyradiculoneuropathy. It has ascending muscle weakness, rapid evolution, the involvement of respiratory muscles with an evolution period of up to four weeks. It has the Classic and Variant forms of clinical presentation. Guillain-Barre Syndrome is a rapidly progressive disease. The diagnosis is clinical but requires exams such as electroneuromyography and cerebrospinal fluid analysis, so that treatment can be started as soon as possible to improve prognosis and increase survival of affected patients.

Acute Nontraumatic Muscle Weakness

AbstractAcute nontraumatic weakness (ANTW) is defined as acute onset of weakness in any part of the body. The weakness occurs due to interruption at any point along the motor pathway. The motor pathway originates from upper motor neuron cells in the cerebral cortex and traverses through the brainstem till lower motor neurons in the spinal cord. The axon of a lower motor neuron is known as the peripheral motor nerve that synapses with muscle. ANTW is of varied etiology and presentation that may be immediately life-threatening if respiratory muscles or autonomic nervous system is involved. Involvement of respiratory muscles may be associated with respiratory failure that may require mechanical ventilation. The weakness may be localized to one limb or generalized involving several muscle groups. When bulbar muscles are involved, weakness leads to problem in swallowing and coughing that endangers the patient's airway. Similarly, the course of the disease also varies, and these patients may worsen rapidly. Hence, a comprehensive history, systematic evaluation, and a detailed neurological examination are performed to localize the disorder. There are specific clinical features peculiar to the particular location of the lesion in the body. Hence, it is possible to anatomically localize these lesions based on the clinical features. Initial laboratory tests and appropriate neuroimaging should be obtained as indicated by history and examination. The time-sensitive emergencies should be addressed immediately, as the delay in management may lead to either permanent neurological damage or may worsen the overall outcome in such conditions. The initial management should always include care of airway, breathing, and circulation (ABC). The imaging should be obtained only after initial stabilization of ABC. The definitive treatment should be done as per the etiology.

Contribution of pulmonary function tests (PFTs) to the diagnosis and follow up of connective tissue diseases

Introduction: Connective Tissue Diseases (CTDs) are systemic autoimmune conditions characterized by frequent lung involvement. This usually takes the form of Interstitial Lung Disease (ILD), but Obstructive Lung Disease (OLD) and Pulmonary Artery Hypertension (PAH) can also occur. Lung involvement is often severe, representing the first cause of death in CTD. The aim of this study is to highlight the role of Pulmonary Function Tests (PFTs) in the diagnosis and follow up of CTD patients. Main body: Rheumatoid Arthritis (RA) showed mainly an ILD with a Usual Interstitial Pneumonia (UIP) pattern in High-Resolution Chest Tomography (HRCT). PFTs are able to highlight a RA-ILD before its clinical onset and to drive follow up of patients with Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO). In the course of Scleroderma Spectrum Disorders (SSDs) and Idiopathic Inflammatory Myopathies (IIMs), DLCO appears to be more sensitive than FVC in highlighting an ILD, but it can be compromised by the presence of PAH. A restrictive respiratory pattern can be present in IIMs and Systemic Lupus Erythematosus due to the inflammatory involvement of respiratory muscles, the presence of fatigue or diaphragm distress. Conclusions: The lung should be carefully studied during CTDs. PFTs can represent an important prognostic tool for diagnosis and follow up of RA-ILD, but, on their own, lack sufficient specificity or sensitivity to describe lung involvement in SSDs and IIMs. Several composite indexes potentially able to describe the evolution of lung damage and response to treatment in SSDs are under investigation. Considering the potential severity of these conditions, an HRCT jointly with PFTs should be performed in all new diagnoses of SSDs and IIMs. Moreover, follow up PFTs should be interpreted in the light of the risk factor for respiratory disease related to each disease.

Diaphragmatic Neurophysiology and Respiratory Markers in ALS.

The main reason for short survival in amyotrophic lateral sclerosis (ALS) is involvement of respiratory muscles. Severe compromise of diaphragmatic function due to marked loss of motor units causes poor inspiratory strength leading to symptomatic respiratory fatigue, and hypercapnia and hypoxemia, often firstly detected while sleeping supine. Weakness of expiratory muscles leads to cough weakness and poor bronchial clearance, increasing the risk of respiratory infection. Respiratory tests should therefore encompass inspiratory and expiratory function, and include measurements of blood gases during sleep. Non-volitional tests, such as phrenic nerve stimulation, are particularly convenient for investigating respiratory function in patients unable to perform standard respiratory function tests due to poor cooperation or facial weakness. However, SNIP is a sensitive test when patients with bulbar involvement are able to perform the necessary maneuvers. It is likely that central respiratory regulation is disturbed in some ALS patients, but its evaluation is more complex and not regularly implemented. Practical tests should incorporate tolerability, sensitivity, easy application for regular monitoring, and prognostic value. Impending respiratory failure can cause increased circulating inflammatory markers, but molecular assessment of respiratory distress requires further study. In future, home-monitoring of patients with accessible devices should be developed.

Prevalence and predictor factors of respiratory impairment in a large cohort of patients with Myotonic Dystrophy type 1 (DM1): A retrospective, cross sectional study

IntroductionRespiratory complications are relevant in DM1, leading to a significantly increased morbidity and mortality risk in these patients; however, so far only few studies concerning respiratory function have been conducted in DM1 patients.We report a retrospective, multicenter, cross sectional study on a large cohort of DM1 patients widely characterized in the phenotype, to assess prevalence and identify predictors of restrictive respiratory syndrome. Methods268 DM1 subjects aged >18 years, who had recently performed spirometric tests were included; restrictive syndrome was diagnosed if forced vital capacity (FVC) <80% of predicted. This cut-off was used for statistical univariate and multivariate analysis. Results51.9% patients showed a restrictive syndrome, and half of them had indication to non-invasive ventilation (NIV), yet only 50% resulted compliant to NIV. CTG expansion size in leukocytes, clinical muscle severity, most functional parameters of respiratory muscle involvement, presence of cardiac conduction disturbances, pacemaker (PMK), exertion dyspnea, obstructive sleep apnea, and indication and compliance to NIV were all significantly associated with restrictive syndrome at the univariate analysis; in the multivariate model only the first two factors resulted independent predictors. DiscussionA high prevalence of restrictive syndrome in our DM1 cohort, mainly due to respiratory muscles weakness, was observed and documented; the severity of muscle impairment and the CTG expansion size confirmed to be independent predictors of respiratory restriction. Our data suggest that optimization of respiratory therapeutic management, particularly regarding launching of NIV, might help to reduce the rate of deaths due to respiratory complications in DM1.

How Different is AMAN from AIDP in Childhood GBS? A Prospective Study from North India.

To compare the clinical profile and short-term outcome of children with axonal and demyelinating subtypes of childhood Guillain Barré syndrome (GBS). This is a prospective observational study conducted in a tertiary care teaching hospital in North India. Consecutive children with Guillain Barré syndrome were recruited to compare the clinical profile and short term outcome among the subtypes. Among 9847 children admitted to the emergency, 95 had acute flaccid paralysis; 57 of whom had GBS. Electrophysiological studies were completed in 57; of whom 20 had acute inflammatory demyelinating polyneuropathy (AIDP); 19 had acute motor axonal neuropathy (AMAN); 12 had non-reactive nerves; five were unclassifiable; 1 had acute motor sensory axonal neuropathy (AMSAN). More children in AMAN group had preceding gastroenteritis (4 vs. 2), while AIDP group had upper respiratory infections (12 vs. 7). Ataxia was only seen in AIDP subtype while wrist drop, foot drop and hyperreflexia were seen only with AMAN subtype. Respiratory muscle involvement (6 vs. 3) and artificial ventilation (5 vs. 2) was more in AMAN. At discharge, children with AIDP were less likely to be non-ambulant (12 vs. 6, p = 0.036). Mean disability scores at hospital discharge (4.9 ± 1.2 vs. 4 ± 0.9, p = 0.015) and at last follow-up (0.7 ± 1.01 vs. 0.05 ± 0.2, p = 0.016) were higher in AMAN. Children with AIDP were more likely to achieve normalcy on follow-up (19 vs. 12, p = 0.023). Children with AMAN appear to have a more severe clinical course; higher short-term morbidity; and slower recovery than those with AIDP.

Thyrotoxic Periodic Paralysis – A Case Report of a Rare Cause of Paralysis in a 39-Year-Old Asian Man

Uncontrolled hyper thyroidism has a myriad of presentations. Classically, symptoms include weight loss, tremor, palpitations, shortness of breath, diarrhea, anxiety, and heat intolerance. A rare manifestation of hyperthyroidism is thyrotoxic periodic paralysis (TPP). Periodic paralysis is a musculoskeletal channelopathy manifested by episodes of painless muscle weakness often precipitated by heavy exercise, fasting, or high carbohydrate meals. Although classically associated with painless weakness; cramping, myalgias, and stiffness can also occur prior to the episodes as prodromal symptoms. Neurologic examination during an attack typically demonstrates proximal more than distal muscle weakness, and the upper extremities are more commonly affected than the lower extremities.1-4 Consciousness and sensation are preserved, and respiratory muscle involvement is exceedingly rare. Episodes of weakness can last from a few hours up to 72 hours with intermittent recovery between attacks. Patients most often have diminished deep tendon reflexes, but reflexes may be preserved in some cases. We present a case of TPP, discuss the differential diagnosis of periodic paralysis, and review the pathophysiology and management of TPP.

Visualizing and Quantifying Thoraco-Abdominal Asynchrony in Children From Motion Point Clouds: A Pilot Study

In a situation of respiratory failure (RF), patients show signs of increased work of breathing leading to the involvement of accessory respiratory muscles and a desynchronization between rib cage and abdomen known as thoraco-abdominal asynchrony (TAA). Proper assessment of these signs requires sufficiently skilled and trained medical staff. However, human assessment is subjective and is practically impossible to audit. A new non-contact method is proposed for TAA visualization and quantification, in children with RF. The surface variations are analyzed by calculating the 3-dimensional motion of the thorax and abdomen regions during the breathing process. A high-fidelity mannequin was used to simulate thoraco-abdominal asynchrony. The proposed system uses depth information recorded by an RGB-D (Red Green Blue-Depth) camera. Furthermore, surface displacement was calculated in four simulated modes from the normal to the severe TAA mode. Respiratory rates were also calculated based on the analysis of the surface movements. The proposed method was compared to a highly precise laser-ranging system with 1 mm resolution. The resulting root mean square deviation (RMSD) showed an error of 1.78 ml in normal mode, 2.83 mm in mild mode, 2.23 mm in severe mode and 2.34 mm in irregular mode. The results showed a high correlation between the two methods in estimating the retraction distance and respiratory rate (ρ >0.985).

Respiratory muscle involvement in sarcoidosis

ABSTRACTIntroduction: In sarcoidosis, muscle involvement is common, but mostly asymptomatic. Currently, little is known about respiratory muscle and diaphragm involvement and function in patients with sarcoidosis. Reduced inspiratory muscle strength and/or a reduced diaphragm function may contribute to exertional dyspnea, fatigue and reduced health-related quality of life. Previous studies using volitional and non-volitional tests demonstrated a reduced inspiratory muscle strength in sarcoidosis compared to control subjects, and also showed that respiratory muscle function may even be significantly impaired in a subset of patients.Areas covered: This review examines the evidence on respiratory muscle involvement and its implications in sarcoidosis with emphasis on pathogenesis, diagnosis and treatment of respiratory muscle dysfunction. The presented evidence was identified by a literature search performed in PubMed and Medline for articles about respiratory and skeletal muscle function in sarcoidosis through to January 2018.Expert commentary: Respiratory muscle involvement in sarcoidosis is an underdiagnosed condition, which may have an important impact on dyspnea and health-related quality of life. Further studies are needed to understand the etiology, pathogenesis and extent of respiratory muscle involvement in sarcoidosis.

Sleep disordered breathing in motor neurone disease.

Motor neurone disease (MND) is a neurodegenerative disease defined by axonal loss and gliosis of upper and lower motor neurones in the motor cortex, lower brainstem nuclei and ventral horn of the spinal cord. MND is currently incurable and has a poor prognosis, with death typically occurring 3 to 5 years after disease onset. The disease is characterised by rapidly progressive weakness leading to paralysis, fasciculations, bulbar symptoms (including dysarthria and dysphagia) and respiratory compromise. Respiratory complications arise as a result of weakness of upper airway (pharyngeal and laryngeal) muscles and respiratory muscles (diaphragm, intercostal and accessory muscles) leading to respiratory failure. Due to early involvement of respiratory muscles in MND, sleep disordered breathing (SDB) occurs at a higher frequency than compared to the general population. SDB usually precedes daytime respiratory symptoms and chronic respiratory failure. It significantly impacts upon patients' quality of life and survival and its presence may predict prognosis. Managing SDB in MND with non-invasive ventilation (NIV) improves quality of life and survival. Early identification and management of SDB in MND patients is therefore crucial. This update will review assessments of respiratory muscle function, types of SDB and the effects of NIV in patients with MND.

Sleep-disordered breathing in patients with neuromuscular disease.

Sleep-disordered breathing (SDB) is relatively common in general population as well as in patients with neuromuscular disease. SDB comprises a wide spectrum of disorders varying from simple snoring to complete closure of the upper airway as seen in obstructive sleep apnoea (OSA). It includes also other disorders like prolonged hypoxemia, hypoventilation, and central sleep apnoea (CSA). Neuromuscular diseases (NMD) form a group of disorders that can cause significant reduction in the quality and span of life. The involvement of respiratory system in the context of these disorders is the most serious complication, and it is considered as the leading cause of death in those patients. NMD can affect ventilation, cough, swallowing, and phonation. The involvement of respiratory muscles makes NMD patients vulnerable to sleep-disordered breathing with a significant prevalence of SDB among such patients.

Practical Recommendations for Diagnosis and Management of Respiratory Muscle Weakness in Late-Onset Pompe Disease.

Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors’ own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease.

Respiratory Muscle Assessment in Acute Guillain–Barré Syndrome

Guillain-Barré Syndrome (GBS) is a life-threatening disease due to respiratory muscle involvement. This study aimed at objectively assessing the course of respiratory muscle function in GBS subjects within the first week of admission to an intensive care unit. Medical Research Council Sum Score (MRC-SS), vigorimetry, spirometry, and respiratory muscle function tests (inspiratory/expiratory muscle strength: PImax/PEmax, sniff nasal pressure: SnPna) were assessed twice daily. GBS Disability Score (GBS-DS) was assessed once daily. On days one (d1) and seven (d7), blood gases and twitch mouth pressure during magnetic phrenic nerve stimulation (Pmo,tw) were additionally evaluated. Nine subjects were included. MRC-SS, vigorimetry, PImax, and SnPna increased between d1 and d7. GBS-DS, spirometry and Pmo,tw remained unaltered. Only SnPna correlated closely with the MRC-SS on both d1 (r=0.77, p=0.02) and d7 (r=0.74, p=0.02). SnPna was the only parameter that correlated with MRC-SS, while the current gold standard of spirometry measurement did not.

A clinical tool for predicting survival in ALS

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age...

D.10 Acute flaccid paralysis in Canadian youth, 1996 to 2014

Background: Acute flaccid paralysis (AFP) is notifiable in Canada with a differential diagnosis that includes a number of conditions. This analysis describes the epidemiology of AFP in Canadian youth less than 15 years old. Methods: Monthly active surveillance for AFP was conducted as part of the Canadian AFP Surveillance System. Results: From 1996 to 2014, 850 cases of AFP were reported, representing an average annual crude incidence rate of 0.77 cases per 100,000 youth less than 15 years old. The mean age of cases was 6.8 years (median 5.9 years). Nine percent had an abnormal neurological history and 53% had an acute respiratory illness within 30 days of onset. Fever occurred in 23% of cases, 96% experienced bilateral weakness, 21% had respiratory muscle involvement, and 26% had cranial nerve involvement. The average hospital length of stay was 13.5 days. The most common diagnoses were Guillain-Barré Syndrome (GBS) or a variant (70%), and transverse myelitis (TM, 14%). At the time of the initial report, 14% had fully recovered. Conclusions: Our AFP surveillance system provides a baseline for AFP and its causes in the Canadian paediatric population. While rare, AFP is associated with severe morbidity in youth. GBS and TM were the most common diagnoses.

625. RNAi Therapy for Dominant Limb Girdle Muscular Dystrophy Type 1A

Limb Girdle Muscular Dystrophy (LGMD) refers to a group of disorders characterized by progressive wasting and weakness of pelvic and shoulder girdle muscles. Patients commonly require wheelchair assistance, and individuals with some forms of LGMD may have cardiac and respiratory muscle involvement. Modest improvements in a limited set of muscles may dramatically improve patients’ quality of life, but currently no effective treatment exists. There are 8 dominant forms of LGMD (LGMD1) that would benefit from gene therapy strategies to reduce their pathogenic alleles. We previously showed the first RNAi-based pre-clinical treatment for LGMD1A, which is caused by dominant mutations in one allele of the myotilin (MYOT) gene. Our strategy involved delivering MYOT targeted artificial microRNAs (miMYOT) to muscles of the T57I transgenic mouse model of LGMD1A using AAV6 vectors. Both 3 months (short-term) and 9 months (long-term) time points showed significant reduction of mutant myotilin mRNA and soluble protein expression. MYOT gene silencing resulted in histological improvements that were accompanied by significant functional correction including increased muscle weight and improved specific force. While the initial study showed proof-of-principle for this therapy, translation of miMYOT requires additional work. Mouse knockout studies suggested MYOT is a non-essential gene, as animals lacking MYOT develop normally. In the case of LGMD1A this would suggest the mutation is harmful but complete loss would be tolerated. However, we do not currently know if haploinsufficiency of wild-type MYOT is tolerated in other organisms, including humans. To address this question, we delivered morpholinos or AAV.miRNAs to multiple species. We found knockdown of endogenous MYOT to be safe in developing Xenopus, adult mice and non-human primates, suggesting that a non-allele-specific silencing approach for MYOT would be tolerated in LGMD1A-targeted treatments. We also performed dose escalations to assess the safety parameters of AAV.miMYOT vectors and utilized microarray data to identify potential biomarkers for clinical outcome measures. We then validated that some of our lead biomarkers were significantly normalized in miMYOT-treated T57I mice. Together these data provide additional data to support the further translation of miMYOT therapy for LGMD1A.