View clinical trials related to Muscular Atrophy, Spinal.
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
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.
Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degeneration of motor neurons in the spinal cord and caused by mutations of the survival motor neuron 1 (SMN1) gene. The investigators will conduct a systematic review of the contents and activities collected via a comprehensive case report form. Patients who fulfilled diagnostic criteria for SMA type 1 will be reviewed retrospectively.
The primary objective of Part 1 of this study is to assess the safety and tolerability of Nusinersen in participants with SMA who are not eligible to participate in the clinical studies ISIS 396443-CS3B (NCT02193074) or ISIS 396443-CS4 (NCT02292537). The secondary objective of Part 1 of this study is to examine the pharmacokinetics (PK) of Nusinersen in participants with SMA. The primary objective of Part 2 of this study is to assess the long-term safety and tolerability of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments. The secondary objective of Part 2 of this study is to examine the PK of Nusinersen in participants with SMA who participated in Part 1 and completed their End of Part 1 Evaluation assessments.
Children with neuromuscular disabilities and limited ambulation are at significant risk for decreased bone mineral density (BMD) and increased incidence of fracture. This is caused, in part, by low levels of load experienced by the skeleton due to a child's functional limitations. Low BMD has been shown to be predictive of fracture, and in fact, fractures usually occur without significant trauma in children with neuromuscular conditions. The discomfort and distress from fractures in this population are considerable, and the associated costs to the family and healthcare system are substantial. Numerous interventions have been devoted to improving BMD in these children. Stationary assisted standing devices are widely used and represent the standard-of-care. However, evidence supporting this approach is limited due to inadequate study designs with insufficient numbers of patients. This study will use load-sensing platforms in patients with neuromuscular conditions. Successful completion of this pilot study will assist in the development of a future multicenter clinical trial to definitively determine relationships, if any, between passive standing and measures of BMD, fracture incidence, pulmonary function, and health-related quality-of-life measures in children with a variety of neuromuscular disabilities (e.g., spinal muscular atrophy, cerebral palsy, muscular dystrophy, spina bifida, Rett syndrome). Hypothesis: Assisted standing treatment program will gradually increase their duration of standing by up to 75% after the baseline phase.
NatHis-SMA is a prospective, longitudinal and interventional study of the natural history of patients with type 2 and 3 Spinal Muscular Atrophy (SMA). The purpose of this study is to characterize the disease course over 2 years and identify prognostic variables of the disease and biomarkers of SMA progression, as well as determine the best outcome measures for further therapeutics approaches.
The primary objective of the study is to examine the efficacy of multiple doses of Nusinersen administered intrathecally in preventing or delaying the need for respiratory intervention or death in infants with genetically diagnosed and presymptomatic spinal muscular atrophy (SMA). Secondary objectives of this study are to examine the effects of Nusinersen in infants with genetically diagnosed and presymptomatic SMA.
Non-ambulatory children with a neuromuscular disability such as spinal muscular atrophy (SMA) are at significant risk for poor bone health as defined by low bone mineral density (BMD) and increased propensity to fracture. Poor bone health is thought to be related, at least in part, to abnormally low levels of load experienced by the skeleton. A common physical approach for increasing bone density is to stimulate the musculoskeletal system by increasing the amount and duration of weight-bearing in the lower extremities. For non-ambulatory individuals, this takes the form of using an assisted standing device to enable the child to spend time in a standing position with some degree of weight placed on the lower limbs. Some of these physical interventions demonstrate variable improvement in BMD in children with neuromuscular conditions, and some do not. A serious limitation in the previous work in this area is a failure to objectively measure the magnitude and duration of the loading experienced by the lower extremities. Thus, a lack of change in BMD may be due to the extremities experiencing only a fraction of the body weight (due to load-sharing with the assistive device) for an inadequate duration of standing time. In order to investigate the efficacy of standing treatment for increasing BMD, the investigators will develop a simple, portable and inexpensive transducer that will measure the magnitude and time course of the load experienced by the lower extremities of individuals with SMA who use a stationary assisted standing device. The specific goal of this proposed project will be to develop, validate and establish the initial feasibility of such a measurement device.