Charcot-Marie-Tooth Disease

Amyotrophic lateral sclerosis ALS is a progressive disease that weakens muscles and often leads to breathing problems, which is the leading cause of death in ALS. This research evaluates the timing and method of starting non-invasive ventilation NIV to assist breathing, as current guidelines vary and are not based on large studies. The study aims to explore early use of NIV in ALS patients before insurance criteria for coverage are met, using a new prediction tool to identify those at high risk of respiratory problems within six months. Participants will be randomly assigned to start early NIV or receive usual care, with the early NIV group receiving ventilation support earlier than current U.S. guidelines suggest. The study will collect data on feasibility, symptoms, carbon dioxide levels, and survival outcomes over about one year. The intervention involves using a ventilation device through a mask to help patients breathe and reduce carbon dioxide in the blood, potentially improving survival. Throughout the study, participants will undergo assessments including quality of life questionnaires, sleepiness scales, breathing function tests, and monitoring of NIV use and hospitalizations. The research team will measure the time to first NIV use, carbon dioxide levels, breathing symptoms, and survival without tracheostomy. Data collected will help plan a larger trial and understand which patients are likely to benefit from early NIV and use it consistently over time.

Researchers are investigating the effects of a multidomain lifestyle intervention to slow cognitive decline and dementia risk in elderly residents aged 60 to 80 in Zhejiang Province, China. The study builds on findings from Finland, where a similar approach combining physical activity, nutrition, cognitive training, social activities, and vascular risk management showed promise in healthy older adults at risk of cognitive decline. This trial aims to explore how such an intervention may change brain structure and function as well as cognitive abilities in an Asian population. Participants are randomly assigned to either a structured multidomain intervention group or a self-guided control group. The intervention group receives tailored nutritional guidance, cognitive training, physical exercises, and vascular risk monitoring, all adapted to Chinese cultural norms. The control group receives regular health education campaigns and basic health monitoring every 6 to 12 months. This trial runs for two years with ongoing assessments to evaluate the impact of these lifestyle changes. During the study, participants undergo various evaluations including cognitive tests measuring global and domain-specific cognition, neuroimaging scans like MRI and fMRI, laboratory blood tests, and physical performance measures such as grip strength and gait speed. Questionnaires assess quality of life, depression, sleep quality, and daily activities. Researchers also monitor cardiovascular health, dementia onset, and falls. This comprehensive monitoring will help determine the interventions effects on brain health and daily functioning over the 24-month period.

Charcot-Marie-Tooth disease type 1A CMT1A is the most common inherited nerve disorder, caused by a gene duplication affecting nerve function. Symptoms typically begin in early childhood and progress variably, but there is currently no established treatment. This research aims to find early disease and prognostic biomarkers in young CMT1A patients by studying gene and protein changes in animal models and translating these findings to humans to better predict disease severity and progression. The study will analyze samples from young CMT1A rats at two timepoints using transcriptomic and proteomic methods to identify early markers. In parallel, children, adolescents, and young adults aged 10 to 30 with CMT1A will be followed for 12 months. Participants will undergo various clinical assessments including novel clinical outcome measures CMTES-R, CMTNSv2-R, functional tests CMT-FOM, nerve conduction studies, quantitative MRI, and patient-reported questionnaires about pain, fatigue, cramps, walking impact, and global change. Blood and optional skin samples will be collected to measure gene expression of promising biomarker candidates. Participants will attend study visits for clinical evaluations, imaging, nerve tests, and sample collection over a year. Researchers will measure changes in clinical scores, functional ability, quality of life, imaging results, and gene expression. Additional analyses include cultivating fibroblasts from skin biopsies for future experiments. This comprehensive approach aims to establish biomarkers for early disease severity and progression, enabling future clinical trials and treatments in young CMT1A patients.

Researchers are studying how muscle and brain interactions relate to neurodegenerative diseases NDGs such as Amyotrophic Lateral Sclerosis, Alzheimers Disease, and Parkinsons Disease, as well as aging. The study explores whether changes at the neuromuscular junction, where muscle and nerve communicate, contribute to these conditions. It aims to identify factors that influence brain-muscle connections and how these may predict disease progression or aging outcomes. This observational case-control study includes two groups a Good Aging group of adults aged 60 or older without muscle or neurological impairments, and a Bad Aging group with patients diagnosed with NDGs or severe acquired brain injury, some with sarcopenia or cognitive issues. Researchers will collect clinical and biological data, including biomarkers, microRNA, and extracellular vesicle analyses, to better understand the muscle-brain relationship and movement issues. Participants will undergo assessments including the Edmonton Frail Scale at the start and after six months to measure frailty changes. The study will gather neurological and muscular phenotyping data to track participants health trajectories. The study spans from baseline to a 6-month follow-up, monitoring physical and cognitive function to inform future clinical strategies for minimizing risks linked to aging and neurological disorders.

Researchers are evaluating anitocabtagene autoleucel anito-cel, a BCMA-directed CAR-T cell therapy, in adults with generalized myasthenia gravis GMG classified as MGFA Grade 2 to 4a. This Phase 1 open-label, multi-center study aims to assess the safety, tolerability, and preliminary efficacy of anito-cel in patients who require immunosuppressive therapy as determined by their neurologist. The study focuses on identifying dose-limiting toxicities DLTs, the maximum tolerated dose MTD, and selecting the recommended Phase 2 dose RP2D for treatment. The study includes sequential phases screening, enrollment with leukapheresis to collect cells, pretreatment with a standard lymphodepletion chemotherapy regimen for 5 days, and a single intravenous infusion of anito-cel cells. Optional bridging therapy may be given while the CAR-T cells are prepared. Following infusion, participants will be closely monitored for safety and efficacy outcomes over time. Participants will undergo safety monitoring for at least 28 days after infusion, with safety data collected throughout the study duration of up to 24 months. Clinical effects will be evaluated using measures including the Myasthenia Gravis Activities of Daily Living MG ADL score, Quantitative Myasthenia Gravis QMG score, and Myasthenia Gravis Composite MGC scale. Additionally, blood tests will monitor autoantibody levels and pharmacokinetics of the therapy. This comprehensive follow-up ensures careful assessment of treatment impact and participant health.

Researchers are studying the safety and effectiveness of a single dose of nexiguran ziclumeran NTLA-2001 compared to a placebo in people with hereditary transthyretin amyloidosis with polyneuropathy ATTRv-PN. This phase 3, multinational, randomized, double-blind, placebo-controlled trial involves about 60 participants with this nerve disease and genetic condition affecting the peripheral nervous system. Participants will be randomly assigned to receive a single intravenous infusion of either nexiguran ziclumeran 55 mg or a placebo of normal saline. To give everyone a chance to receive the study drug, participants may switch to the other treatment group at either 12 or 18 months, depending on specific study criteria. The study is designed to compare the effects of the drug and placebo over time. During the study, participants will be monitored for nerve function using the Modified Neuropathy Impairment Score 7 mNIS7 over 18 months and blood levels of serum transthyretin at 29 days and 18 months. Quality of life, body mass index, and other health measures will also be evaluated. The study includes careful safety monitoring and will last up to 18 months with ongoing assessments to track participants nerve health and overall well-being.

Researchers are conducting a Phase 3 clinical trial to evaluate the safety and effectiveness of AOC 1044, also known as delpacibart zotadirsen, for treating Duchenne Muscular Dystrophy DMD in boys aged 7 to 16 with specific gene mutations suitable for exon 44 skipping. This study is designed as a randomized, double-blind, placebo-controlled trial to assess the impact of this intravenous treatment on muscle function over time. Participants will be randomly assigned to receive either AOC 1044 or a placebo infusion every 6 weeks for 54 weeks, totaling 9 doses during the double-blind treatment period. After this, all participants can join an open-label extension where they receive AOC 1044 every 6 weeks for another 54 weeks, adding 9 more doses. Following the final dose at week 102, participants will have assessments at weeks 108 and 114 to evaluate safety and treatment effects. During the study, participants will undergo various assessments including tests for time to rise velocity, muscle strength, walking and climbing abilities, and quality of life measures. Muscle enzyme levels and global impressions of severity and change from both patients and caregivers will also be monitored. Safety and tolerability will be reviewed regularly by an independent committee. Overall participation lasts over two years, including screening, treatment, extension, and follow-up phases.

This research aims to analyze natural history data from patients with Charcot-Marie-Tooth disease and related disorders in China. It focuses on assessing clinical, genetic, and epigenetic features to better understand the condition and improve clinical management. The study is observational and gathers detailed information to support patient care optimization. Participants include patients clinically or genetically diagnosed with Charcot-Marie-Tooth disease and unrelated healthy controls. The study collects data over time to observe disease progression and characteristics without administering any treatments or interventions. Throughout the study, researchers will monitor changes in the Charcot-Marie-Tooth Neuropathy Score CMTNS over up to six months. Participants will undergo assessments that help track the diseases impact and progression. The study is open to all genders and ages, with voluntary participation and long-term observation planned until the study end date in 2049.

Researchers are studying how nerve test results change in people with urothelial carcinoma who are treated with enfortumab vedotin. This observational study focuses on assessing nerve function and patient-reported neuropathy in individuals with metastatic or muscle-invasive urothelial carcinoma. The study is led by Memorial Sloan Kettering Cancer Center and aims to understand chemotherapy-induced peripheral neuropathy linked to this treatment. Participants will undergo non-invasive nerve conduction studies to objectively measure nerve function, especially in sensory fibers affected by neuropathy. They will also provide self-reported information about their neuropathy symptoms. The study includes individuals planned to start systemic therapy with enfortumab vedotin, with or without pembrolizumab. During the study, nerve conduction tests and questionnaires about neuropathy will be collected from baseline up to 9 to 15 weeks. Researchers will monitor changes in nerve function and neuropathy severity over this period. Participants must be able to communicate in English and have a performance status allowing study participation. The study does not involve therapeutic interventions but focuses on observation and assessment of nerve health during treatment.

Researchers are evaluating the effectiveness of Acceptance and Commitment Therapy ACT-based group therapy for improving mental health in people with mixed neurological disorders, including those with post-COVID conditions. These disorders often involve cognitive difficulties that can affect psychotherapy outcomes. This study focuses on whether the therapy improves mental health symptoms and how executive functions, especially abstract thinking, relate to social participation and mental health after therapy. The study involves an ACT-based group therapy program adapted from a manual for neurological conditions. Participants join groups of three to six people and attend eight weekly 100-minute sessions led by licensed psychotherapists. Before the therapy, participants spend eight weeks on a waiting list. The therapy uses metaphors and imagery and aims to improve psychological flexibility. Participants will be assessed before and after the waiting list period and therapy using various psychological tests and questionnaires measuring depression, anxiety, stress, and cognitive functions. Researchers will monitor therapy motivation, cognition, and language ability. The total participation includes the waiting period and therapy sessions, with outcomes measured approximately eight weeks apart to evaluate changes in mental health and executive function.