View clinical trials related to Motor Neuron Disease.
Filter by:The purpose of this study is to collect CSF and blood samples that can be used in future research studies to identify potential biomarkers in blood and cerebrospinal fluid (CSF) collected in Amyotrophic Lateral Sclerosis (ALS) patients.
Amyotrophic lateral sclerosis (ALS), is a rapidly progressive neurodegenerative disorder, usually leading to death from respiratory failure in 3-5 years. Riluzole, the only drug currently available, only modestly prolongs survival and does not improve muscle strength or function. In ALS, loss of functional motor neurons is initially compensated for by collateral reinnervation and strength is preserved. In the majority of ALS patients, as the disease progresses, compensation fails leading to progressive muscle weakness. Conversely, in long-term ALS survivors, slow functional decline is correlated with their ability to maintain a successful compensatory response to denervation over time. Compensatory collateral reinnervation is thus essential for functional motor preservation and survival, and elucidation of the molecular mechanisms involved is crucial to help identify new therapeutic targets. Energy metabolism and glucose homeostasis modifications also influence disease clinical course but the mechanisms by which they contribute to the progression of ALS are unknown. Weight loss is an independent negative prognostic factor for survival and, by contrast, ALS risk and progression are decreased in individuals with high body mass index and non-insulin-dependent diabetes mellitus. Insulin shares many common steps in its signaling pathways with insulin-like growth factor 1 (IGF-1), and is thus at the interface between glucose homeostasis regulation and maintenance of muscle mass. However, the contribution of insulin signaling to preservation of muscle innervation and function in ALS has never been investigated. With this study, we aim to determine the role of insulin signaling pathways in maintenance of collateral reinnervation and muscle function in ALS. We will also investigate the link with the disease-modifying effect of metabolic and glucose homeostasis perturbations, by identifying the contribution of metabolic profiles to preservation of skeletal muscle innervation and motor function in patients with ALS. For this purpose, we will determine the whole-body and skeletal muscle metabolic profiles of 20 patients with ALS and correlate these results to collateral reinnervation ability quantified on muscle biopsy specimens. For each patient, we will use both clinical and electrophysiological methods to evaluate motor function and motor neuron loss over time. Body composition, insulin secretion, insulin resistance level and serum concentrations of IGF-1 axis components will be determined. A motor point muscle biopsy will be performed for morphological analysis of neuromuscular junctions and quantification of innervation by confocal microscopy. Activation of insulin/IGF-1 canonical signaling pathways and metabolic pathways of glucose homeostasis will be quantified in muscle specimens. Skeletal muscle and whole-body metabolic parameters will be analyzed together and correlated with clinical assessment of motor function, electrophysiological data, and innervation quantification results. For comparison, 10 healthy subjects of similar age and 10 patients with spinal and bulbar muscular atrophy - a slowly progressive motor neuron disorder with maintenance of effective collateral reinnervation - will be used as controls. This study will be the first to address the question of the contribution of insulin signaling pathways and metabolic profiles in maintenance of muscle reinnervation and function in ALS patients. The molecular mechanisms identified will be new targets for future treatments promoting compensatory reinnervation and slowing disease progression in ALS. Ultimately, this translational project could have a significant therapeutic impact in disorders with muscle denervation and collateral reinnervation as a compensatory mechanism, such as spinal muscle atrophy or peripheral neuropathies.
The investigators seek to validate Slow Vital Capacity (SVC) measurement in seated and supine positions using conventional and portable spirometry.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition, mainly characterized by progressive weakness and wasting of the limbs, the respiratory and bulbar muscles. Respiratory insufficiency leads to a fatal outcome after a mean diseases duration of only three to five years. The disease is characterized by pathological accumulations of a protein called TDP-43, which can be found large cortical and sub-cortical areas of post-mortem ALS brains. No causal treatment for this condition is known to date, and there is a large unmet need to develop new strategies in order to halt or slow down its progression. The aim of this study is to test the safety and tolerability of Tideglusib, a treatment that is already in clinical trials for other neuromuscular conditions, in patients with ALS. It is assumed that this drug may have a significant therapeutic benefit in this population due to his mode of action: In the ALS mouse model, Tideglusib decreases significantly the amount of accumulated TDP-43 proteins within the cells.
The specific aims of this study are to: 1. Determine if a painless and quick measurement of muscle activity using surface electrodes can help with the diagnosis of ALS. Specifically, we ask if a measure of intermuscular coherence (IMC-βγ), when added to current diagnostic criteria (Awaji criteria), can differentiate ALS from mimic diseases more accurately and earlier than currently possible. 2. Characterize IMC-βγ in neurotypical subjects by age, sex, race, and ethnicity. 3. Follow a cohort of ALS patients longitudinally to determine if IMC-βγ changes with ALS disease progression and whether such changes correlate with functional and clinical scores, or survival.
Amyotrophic lateral sclerosis (ALS) is a serious rapidly progressive disease of the nervous system. The mean survival from the time of diagnosis is 2.5 years. Apart from Riluzole, there is no effective treatment. Care of advanced ALS will have a cost of 4-8 million NOK (Norwegian kroner) per year. Research i.a. from the investigators department has shown that increased activity in histone deacetylation enzymes (sirtuins) together with increased access to Nicotinamide Adenine Dinucleotide (NAD) can delay disease progression. Nicotinamide riboside (NR) can increase cells' access to NAD and Pterostilbene will stimulate sirtuins. The investigators want to study whether combination therapy with NR and Pterostilbene can inhibit neurodegeneration in ALS and thereby delay disease development, increase survival and improve quality of life in ALS. In the NO-ALS extension study the investigators will follow the patients who completed the original NO-ALS study. Objectives are to evaluate adverse events and give patients possibility of compassionate use, and secondarily to see if the combination of NR and pterostilbene (EH301) will decrease progression of motor symptoms and loss of vital capacity, and increase survival time in patients with ALS.
The aim of the study is to evaluate the interest of the determination of pNFH and NFL neurofilaments in serum for the diagnosis of ALS in patients with a diagnostic standoff after evaluation in an expert ALS center. The hypothesis is that one of these biomarkers, or their combined analysis, will make it possible to confirm or invalidate the diagnosis of ALS.
Amyotrophic Lateral Sclerosis (ALS), often referred to as Lou Gehrig's Disease, is a progressive, terminal condition of muscle weakness that is associated with degeneration of neurons in the spinal cord and brain. This devastating disorder afflicts people in the prime of their lives. At the present time, there are no cures for this disorder, and current treatments are marginal at best. Despite years of intensive research, a fundamental understanding of this disease is still lacking. There is a need to identify both reliable markers of disease progression and effective treatments. The goal of this research is to bring a greater understanding of ALS patients closer to the research studies that can lead to new hypotheses and approaches.
A phase 2 double-blind, placebo-controlled study of AL001 in participants with C9orf72-associated ALS.
The Synchron Motor Neuroprosthesis (MNP) is intended to be used in subjects with severe motor impairment, unresponsive to medical or rehabilitative therapy and a persistent functioning motor cortex. The purpose of this research is to evaluate safety and feasibility. The MNP is a type of implantable brain computer interface which bypasses dysfunctional motor neurons. The device is designed to restore the transmission of neural signal from the cerebral cortex utilized for neuromuscular control of digital devices, resulting in a successful execution of non-mechanical digital commands.