Spinal Muscular Atrophy (SMA)

The 100-Year Human Aging Study is a long-term observational research project enrolling adult participants to undergo detailed multi-system health screenings and follow them throughout their lives until death. The study aims to identify which health measurements taken at enrollment and repeatedly over time can predict overall mortality, cause-specific death, serious diseases, and functional disability. It addresses the current lack of validated longevity measures by generating data on how various physiological and cognitive functions relate to aging outcomes. Participants undergo a comprehensive clinical screening that includes tests of cardiorespiratory fitness, strength, mobility, neurocognitive performance, sensory functions, and metabolic health. Structural imaging assessments like DEXA scans, echocardiography, electrocardiography, spirometry, retinal photography, and vascular ultrasound are performed. Laboratory tests and detailed medical, social, and environmental histories are also collected. The study allows participation from single tests up to a full two-visit screening, with repeat testing encouraged to track health changes over time. Throughout the study, participants receive individualized reports with investigational estimates of biological age and predicted mortality risks, which are being evaluated against actual health outcomes. Researchers collect data continuously on mortality, disease occurrence, disability, and health behavior changes. The study involves ongoing follow-up with periodic assessments and aims to preserve all collected data for future analyses, with participant involvement potentially spanning their entire lifespan.

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 evaluating a group intervention called Lev-g, designed to promote healthy habits in individuals with neurodevelopmental disorders or those closely related to children with disabilities. This brief, transdiagnostic, interprofessional program addresses health-related habits that influence mental and physical health, aiming to provide a usable model across various healthcare settings in Sweden. The study focuses on understanding the feasibility, acceptability, and potential effects of this intervention in improving health behaviors. Lev-g consists of three group sessions plus a booster session, employing psychoeducation, motivational interviewing, and applied behavioral analyses. The group format aims to provide peer support and sharing of tips among participants. There is no control group, as this trial tests the feasibility of the intervention. The program is delivered in healthcare settings and is intended for adults aged 15 to 80. Participants will be assessed for completion rates, satisfaction, treatment credibility, adverse events, and goal achievement throughout and after the intervention. Evaluations include questionnaires for both participants and healthcare workers at multiple time points up to 3 to 4 months. Researchers will measure well-being, self-efficacy, and changes in health-related habits, tracking progress from baseline through the booster session. The study is expected to conclude by early 2027.

Researchers are comparing two models of robotically assisted rehabilitation to find the best approach for people with spinal muscular atrophy SMA aged 0 to 21 years. This single-center, randomized, single-blinded study aims to determine which rehabilitation model works better depending on the patients age and starting physical abilities. The study plans to include 200 patients, with 100 in each rehabilitation group. The study involves two rehabilitation methods Robotically Assisted Verticalization and Robotically Assisted Locomotion. Both approaches include motor control training, locomotion with balance and coordination exercises, verticalization training using standing frame devices, and cognitive therapy. The trial will last for up to 4 years, with patients randomly assigned to one of the two rehabilitation groups. Participants will undergo regular clinical assessments using several tests including the Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders, motor function scales, gait and balance tests, and imaging of the spine and hip joints. Quality of life for patients and their caregivers will also be evaluated. These assessments occur every six months for up to 2.5 years. The study will monitor hospitalizations, discomfort during therapy, and fracture occurrences throughout the trial period.

Researchers are conducting a long-term safety study to observe Brazilian pediatric patients diagnosed with Spinal Muscular Atrophy SMA who have been treated with Onasemnogene Abeparvovec Zolgensma. This observational study collects real-world safety data for up to 15 years after treatment, supporting ongoing benefit-risk assessment and monitoring for new safety signals as required by Brazilian Health Authority ANVISA. The study involves pediatric patients with SMA who have already been treated with Onasemnogene Abeparvovec. It is non-interventional, meaning patients continue their usual care while researchers observe and collect data. Participants may be enrolled on the day of treatment or retrospectively if prior medical history is available. No new treatments are assigned, and there is no control or placebo group. Participants and their caregivers will be followed for up to 15 years through phone contacts and medical assessments to monitor safety events, survival, ventilatory support needs, and developmental milestones. Researchers will evaluate treatment-emergent serious adverse events within the first 5 years and track several secondary outcomes including adverse events of special interest, survival without permanent ventilatory assistance, and achievement of motor and developmental milestones over the full 15-year period.

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.

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.

Spinal and Bulbar Muscular Atrophy SBMA is a rare condition with no current cure to stop or slow its progression. Researchers are studying the potential of beta2-agonist drugs, specifically clenbuterol, to improve muscle function in people with SBMA. This phase II, multicenter, randomized, double-blind, placebo-controlled trial aims to evaluate the safety and effectiveness of clenbuterol for this condition, addressing concerns from earlier small-scale studies. In this trial, 90 participants with genetically confirmed SBMA will be randomly assigned to one of two groups. One group will receive clenbuterol tablets at a dose of 0.04 mg per day, while the other group will receive placebo tablets. Both groups will be treated for 48 weeks under a quadruple-blind design to compare the effects of clenbuterol against placebo. Participants will be involved for 48 weeks during which their motor function and quality of life will be closely monitored. Assessments include a 6-minute walk test, SBMA-FRS scale, Adult Myopathy Assessment Tool, lung function tests, serum creatinine levels, and neuromuscular quality of life questionnaires. Safety and efficacy data collected will help determine the potential benefits and risks of clenbuterol in SBMA patients.