View clinical trials related to Muscular Atrophy.
Filter by:The primary objective is to evaluate the long-term safety and tolerability of nusinersen (ISIS 396443) administered by intrathecal (IT) injection to participants with Spinal Muscular Atrophy (SMA) who previously participated in investigational studies of nusinersen. The secondary objective is to examine the long-term efficacy of nusinersen administered by IT injection to participants with SMA who previously participated in investigational studies of nusinersen.
Creation of a large repository of induced pluripotent stem cells (iPSC), bio-fluid samples (blood and spinal fluid (optional)), and cell lines for ALS gene identification. This will be combined carefully with collected measures of the pattern of the symptoms people with ALS have and how these change over time. People with other motor neuron diseases and healthy controls will be included as comparisons
To investigate the effects of different dietary regimens on muscle wasting, insulin/IGF-1 resistance. Further, to explore whether LPD+KA decrease the activation of autophagy associate with insulin/IGF-1 pathway.
One third of independent older adults over the age of 65y will be hospitalized for an acute medical illness, injury, or operative procedure. Unfortunately, 50% of these older adults will experience functional decline during their hospital stay from the amount of time they are physically inactive and in bed. Following discharge, the functional deficits can persist for months and in many instances never return to pre-hospitalization levels thus compounding morbidity, health care costs and dying. A classic consequence of short-term bed rest in older adults is the significant loss in skeletal muscle mass which underlies the accelerated leg strength deficits. The investigator has shown that an important mechanism of skeletal muscle loss is the inability of nutrients to stimulate a normal muscle protein synthesis response; a process highly regulated by the mammalian target of rapamycin signaling pathway (mTOR) and amino acid transporters. Day to day maintenance of force generating muscle tissue is dictated by anabolic stimulation from muscle contraction and essential amino acid ingestion. Therefore, anabolic interventions such as neuromuscular electrical stimulation (NMES) and high quality protein supplementation that contains a high proportion of essential amino acids (whey protein) may be promising approach to maintain leg muscle mass and strength in hospitalized older adults and prevent the long term consequences of repeated periods of short-term physical inactivity. The purpose of this study is to test in older adults if the combination of NMES and protein supplementation is capable of preserving muscle mass and strength and maintaining muscle nutrient anabolic sensitivity during bed rest. The investigators current hypotheses are that daily NMES and protein supplementation during 5-days of bed rest in older adults will: 1) preserve lower extremity muscle mass and strength and 2) maintain muscle nutrient anabolic sensitivity as measured by mTOR signaling and amino acid transporter expression. The long term goal is to utilize this inpatient preventative therapeutic approach in a clinical setting in which muscle mass and strength deficits are profound (e.g., intensive care patients).
Intensive care unit acquired muscle weakness (ICUAW) is a common disease. After 7 days of mechanical ventilation, a quarter of patients develop an ICUAW responsible of a 15-20% of muscle loss. This is a serious pathology associated with high morbidity and mortality. Clinical diagnosis of ICUAW is difficult and need a patient awoken. CT scan and Magnetic Resonance Imaging (MRI) are considered as "gold standards" to quantify and monitor changes in muscle mass. But these tools are not adapted to ICU patients. Ultrasound (US) is an easy access tool at the bedside to assess muscle mass and does not expose the patient to additional radiation. The objective of this study is to evaluate the correlation between US and CT scan to measure quadriceps muscle thickness of ICU patients.
Aim of the present study is to determine whether muscle mass as assessed by bioelectrical impedance analysis correlates with and corresponds to muscle mass as assessed by CT scan analysis in critically patients admitted to the intensive care unit.
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder characterized by loss of motor neurons in the anterior horn of the spinal cord and leading to muscle atrophy. SMA has an autosomal recessive inheritance and affects 1 in 6000 infants with a carrier frequency of 1 in 40. In most cases, it is caused by homozygous gene deletion or gene conversion of the SMN1 gene (0+0 genotype) on 5q11-q13. This genomic region has been duplicated and inverted during evolution. Thus the SMN1 gene has a very homologous copy, called SMN2. Genetic counseling aim at detecting carriers with only one copy of the SMN1 gene (0+1 genotype). SMA carrier testing relies on total copy number quantification of the SMN1 copies by quantitative PCR methods. Nevertheless, cis-duplication of the SMN1 gene on one allele and deletion on the second allele (2+0 genotype) can lead to a misinterpretation as molecular methods show 2 copies of the SMN1 gene and cannot detect the carrier status. The aim of the study is the characterization of a biomarker specific of the cis-duplication of the SMN1 gene in order to allow the detection of this 2+0 genotype which constitutes a trap for genetic counseling. We will use molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. The characterization of this GMC is based on the comparison of two sample groups: - The test group, with a maximum of 137 individuals carrying 3 copies of the SMN1 gene (suggesting a cis-duplication on one allele) - The control-1 group, with a maximum of 137 individuals carrying 2 copies of the SMN1 gene A pilot study performed on 24 samples in the two groups is needed to define the exact sample number necessary for statistical analysis of the study. When the GMC will be characterized, its specificity will be evaluated by testing two sample groups: - The test group, with 37 individuals carrying 3 copies of the SMN1 gene - The control-2 group, with 37 individuals carrying 3 copies of the SMN2 gene Molecular combing needs long DNA fibers and usual methods for DNA extraction are not appropriate. This project requires new blood samples for specific DNA extraction. If this project is successful, during a second project, this GMC will be converted into a simple and cheap PCR-based method. We will then evaluate the sensitivity of this method on our sample collection, notably on individuals with the 2+0 genotype defined by familial genotyping.
The goal of this study is to establish a genetic registry of patients with early-onset motor neuron and neuromuscular diseases. The investigators will collect samples from patients with a motor neuron or a neuromuscular disorder and their family members. The samples to be collected will be obtained using minimally invasive (whole blood) means. The research team will then extract high quality genomic DNA or RNA from these samples and use it to identify and confirm novel gene mutations and to identify genes which regulate the severity of motor neuron/neuromuscular diseases.
Muscle size declines at around 0.5-1% per year after 50 years of age, with muscle strength declining up to twice as fast as muscle size. This may eventually lead to loss of independence if tasks of daily living become too strenuous to be performed safely. Short periods of bed rest cause very rapid loss of muscle size and strength, and studies using healthy older participants have shown that age increases vulnerability to this muscle loss. However, it is unlikely that healthy individuals would be faced with periods of bed rest unless suffering a severe illness. In light of this, recent evidence has shown that even just reducing walking to less than 1,500 steps per day for two weeks caused 4% loss of leg muscle in over 65 year olds. This amount of activity is roughly the equivalent of being housebound, something that may become more common into older age, for example due to prolonged bad weather, or minor injury or illness. This study will investigate what causes such stark muscle loss during two weeks of reduced activity, and the impact on skeletal muscle function and size, as well as balance, body composition, and other indicators of general health such as how the body responds to food or exercise. Importantly, exercise strategies that could reduce muscle loss during a period of reduced activity will also be investigated. In brief, three groups of 10 older men (aged 65-80 years) will undertake two weeks of reduced physical activity by limiting their daily steps to <1,500/day. All groups will then undertake a re-training exercise programme to ensure that any losses in muscle strength or size are regained. One of the groups will be a control, whereby they will undertake the step-reduction intervention and re-training, but no protective exercise before or during the step-reduction intervention. This group will allow us to achieve our primary objective of determining the influence of two weeks of reduced physical activity on muscle strength and size in healthy older males. The two other groups will undertake either four weeks of strength exercise training before the step-reduction intervention, or daily home based exercise 'snacking' during the step-reduction intervention. The potential protective benefits of the exercise interventions in reducing the impact of two weeks of reduced activity on muscle strength and size, and any effect on how muscle is re-gained afterwards, will be compared to the 'control' group.
This study aims to determine whether vitamin D3 supplementation is any more effective in improving musculoskeletal function when combined with exercise training compared with exercise training alone.