Active clinical trials for "Motor Neuron Disease"

Genetic diagnosis of Amyotrophic Lateral Sclerosis (ALS) could identify the origin of the disease, potentially allowing the patient to pursue targeted/gene therapy. However, many familial forms of ALS are genetically undiagnosed, either because no variant has been detected in the genes of interest, or because the detected variant(s) have uncertain significance. Currently, molecular diagnosis takes place in two stages: 1) Search for the GGGGCC expansion in the C9ORF72 gene by RP-PCR; 2) Analysis of the coding regions by high-throughput sequencing of a panel of 30 genes involved in ALS. Many of these variants of uncertain significance affect splicing. Their impact can be predicted using in silico tools, but only an analysis of the patient's RNA can confirm their pathogenic nature. Currently, the analysis of transcripts is only done a posteriori, when a variant predicted to impact splicing is detected on the patient's DNA. RT-PCR followed by Sanger sequencing then verifies the impact of the splice variants. This method confirmed the impact of certain splice variants in patients. However, this method is time-consuming and requires custom development, and is mutation/gene/patient-dependent. In contrast, high-throughput RNA sequencing (RNA-Seq) simultaneously analyzes the splicing of numerous genes, with a global approach, applicable to all patients. This approach avoids the custom design of primers, which can be biased by the interpretation of splicing predictions, while RNA-Seq systematically captures and sequences all the transcripts. Finally, RNA-Seq provides additional information compared to DNA sequencing such as the detection of exon skipping, intron inclusion, and the creation of fusion transcripts. In the GTEx project (GTEx Consortium, 2013), expression levels of human genome transcripts were quantified by RNA-Seq. Using these results, the study investigators measured expression of transcripts of known ALS genes in whole blood. Applying a threshold value of 0.5 transcripts per million reads (TPM), 25 of the 30 ALS genes currently analyzed by NGS in routine diagnostics at Nîmes University Hospital could be eligible for a complete analysis by RNA-Seq. None of the French laboratories carrying out genetic analyzes of ALS has yet developed RNA-Seq as a routine diagnostic tool. The study laboratory receives more than 600 requests for genetic diagnosis of ALS patients per year. The aim of this study is therefore to develop a global method for analyzing RNA transcripts of ALS genes to categorize the mutations to improve the diagnostic management of patients.

The purpose of this study is to evaluate the safety of intramuscular (IM) administration of Engensis in Participants with Amyotrophic Lateral Sclerosis (ALS) as compared to Placebo. Safety will be assessed by incidences of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), injection site reactions (ISRs) and other adverse events of special interest (AESIs), and the clinically significant laboratory values after injections of Engensis compared to Placebo. Exploratory endpoints include assessment of muscle function using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and ALSFRS-R subscores for Fine and Gross Motor Function; muscle strength by quantitative testing using handheld dynamometry (HHD) and the Accurate Test of Limb Isometric Strength (ATLIS) where available; quality of life using the ALS Assessment Questionnaire (ALSAQ-40); patient global impression of change (PGIC), clinical global impression of change (CGIC), and clinical global impression of severity (CGIS); and evaluation of lung function using Slow Vital Capacity (SVC). Muscle biopsies will be performed during the study for future biomarker analyses.

The goal of this study is to evaluate the safety of using the [5-cyano-N-(4-(4-[11C]Methylpiperazin-1-yl)-2-(Piperidin-1-yl)Phenyl)Furan-2-carboxamide] ([11C]CPPC) radiotracer in positron emission tomography (PET) imaging of people with amyotrophic lateral sclerosis (ALS). The investigators are also interested to see whether use of this radiotracer reveals imaging differences between patients with ALS and healthy patients.

MetFlex is an investigator led, open-label, single-arm, Phase 2a trial to determine the safety and tolerability of trimetazidine for the treatment of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND).

This will be a 6-month, widely inclusive, virtual, single-center, open-label pilot trial utilizing a historical control group.

Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Current drugs approved for ALS treatment only modestly slow disease progression. Transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebral excitability in several neurodegenerative disorders and modulate intracortical connectivity measures. In this randomized, double-blind, sham-controlled study followed by an open-label phase, the investigators will evaluate whether a repetition of two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS, after a six months interval, may further outlast clinical improvement in patients with amyotrophic lateral sclerosis and can modulate intracortical connectivity, at short and long term.

Dyspnea; subjective experience of respiratory discomfort; which produces negative emotional experience, is the most common symptom of patients afflicted with chronic respiratory failure and its treatments are limited. Amyotrophic Lateral Sclerosis (ALS) related - dyspnea, due to diaphragmatic dysfunction, is similar to dyspnea during mechanical inspiratory load (activation of the supplementary motor area, SMA). The perception of pain and dyspnea is processed in similar brain areas (insula, dorsal anterior cingulate cortex, amygdala and medial thalamus) and in ALS; relieving dyspnea by noninvasive ventilation (NIV) is associated with decreased pain thresholds. Otherwise, it is reported systemic elevations of pro-inflammatory cytokines in chronic pain patients, correlating with intensity of pain, and during respiratory load in healthy volunteers. The objectives are to evaluate the cytokines and endorphins rates variations after initiation of NIV in ALS patients, and to correlate cytokines and endorphins rates with the intensity of the affective component and the intensity of the sensory component of dyspnea. The investigators will perform a prospective, experimental study, including 30 ALS patients. Dyspnea, ventilatory and cardiac settings, electromyographic recording of the scalene muscle and biological assays (ACTH, endorphin, Neuropeptide P, BDNF, IL1, IL6, IL8, IL10, TNF), will be measured during spontaneous breathing and during NIV at different times after initiation. The investigators expect a reduction of immunological and neurobiological markers after relieving dyspnea by NIV. This work could lead to the development of new treatments for dyspnea.

The purpose of this study is to assess the safety and tolerability of clenbuterol (taken by mouth) in subjects with ALS (amyotrophic lateral sclerosis) and to assess the effectiveness of clenbuterol with regard to motor function in subjects with ALS. Subjects will be in this study approximately 24 weeks. The study drug, clenbuterol, is taken twice a day. As part of this study subjects will have the following tests and procedures: medical history, vital signs, physical examination, blood tests, heart and lung function tests, muscle function test, ALSFRS-R (ALS Functional Rating Scale Revised), thyroid function and for women who can become pregnant, pregnancy tests.

VA research has been advancing a high-performance brain-computer interface (BCI) to improve independence for Veterans and others living with tetraplegia or the inability to speak resulting from amyotrophic lateral sclerosis, spinal cord injury or stoke. In this project, the investigators enhance deep learning neural network decoders and multi-state gesture decoding for increased accuracy and reliability and deploy them on a battery-powered mobile BCI device for independent use of computers and touch-enabled mobile devices at home. The accuracy and usability of the mobile iBCI will be evaluated with participants already enrolled separately in the investigational clinical trial of the BrainGate neural interface.

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. Regimen E will evaluate the safety and efficacy of a single study drug, SLS-005 (Trehalose injection, 90.5 mg/mL for intravenous infusion) in participants with ALS.