Spinal Muscular Atrophy (SMA)

Researchers are conducting the 100-Year Human Aging Study, an observational trial designed to follow participants over their lifespans to investigate which health measurements can predict mortality, serious diseases, and functional disability. The study aims to validate many longevity measures that currently lack prospective evidence by tracking physiological, cognitive, social, and environmental factors that change with aging. This research will generate important data to improve understanding of aging and longevity medicine. Participants undergo comprehensive multi-system clinical screenings including tests like cardiopulmonary exercise testing, body composition assessment by DEXA, echocardiography, electrocardiography, spirometry, neurocognitive testing, sensory assessments, metabolic testing, and detailed medical and social histories. The study allows for different levels of participation, from single tests to full two-visit screening batteries, and encourages repeat testing to capture health changes over time. During the study, participants receive individualized reports including investigational estimates of biological age and predicted cause of death. Researchers collect data on mortality, serious health events, chronic diseases, functional ability, and lifestyle changes through periodic follow-up over many years, potentially up to 100 years. This extensive data collection helps evaluate how well these measurements predict aging outcomes. All data are stored in raw form for future analysis and participants are supported with ongoing contact and opportunities for repeat assessments.

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 patient's 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 Children's 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 intervention's 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 (mNIS+7) 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.

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.

Researchers are conducting a multicenter, prospective observational study to understand the natural history of Charcot-Marie-Tooth Disease, Type 4J (CMT4J), a rare neurodegenerative and neuromuscular condition confirmed by specific genetic testing. The study will enroll 20 participants of any age who have a molecularly confirmed diagnosis of CMT4J. The purpose is to collect detailed health information and disease progression data over time, without providing any investigational treatments. Participants will follow a uniform protocol with visits scheduled every 12 months plus a 4-week window, for up to 2 years. At each visit, researchers will collect demographic and medical history data, perform physical and neurological exams, standard lab tests, and use several disease outcome measures. Additional assessments may include neuropsychological tests, nerve conduction studies, muscle MRI, pulmonary function tests, and scoliosis x-rays. Early termination visits are planned if participants leave before completing the study. Throughout the study, participants will undergo thorough evaluations to monitor their condition and collect data relevant to CMT4J progression. This includes clinical exams, imaging, lab tests, and questionnaires. Researchers will use this information to study disease patterns and outcomes over the 2-year follow-up period. No investigational products are administered, and visits may be unscheduled if necessary with approval. Participants are expected to comply with study procedures and travel requirements.

Researchers are studying older adults aged 65 and above who are pre-frail or mildly frail to evaluate the effects of Whole Body Vibration Training (WBVT) combined with usual care compared to usual care alone. This trial aims to improve muscle mass, strength, and function, addressing the challenges of traditional exercise programs that many older adults find difficult to follow due to physical or cognitive limitations. The study focuses on measuring muscle strength and physical function changes after interventions. Participants will be randomly assigned to one of two groups: one group will receive WBVT along with usual care, and the other will receive only usual care. WBVT sessions use the Galileo Vibration machine three times a week for four weeks, progressively increasing vibration frequency, squat angles, and session duration. Both groups will receive instruction on Otago exercises to be done at home, with encouragement to continue aerobic activities like brisk walking. Exercise and falls diaries will be kept for up to three months. Participants will undergo assessments before the intervention, two weeks after, and three months after. These include measurements of knee extension strength, hand grip strength, muscle mass, gait speed, chair stands, calf circumference, physical activity levels, and quality of life. Falls, emergency visits, hospitalizations, and mortality will also be tracked for one year. The study includes surveys and interviews to evaluate feasibility and accessibility, with adherence monitored by reminders and diaries.

Spinal muscular atrophy (SMA) is a genetic condition that leads to weakening and wasting of muscles due to loss of nerve cells in the spinal cord. This registered cohort study focuses on individuals in China with SMA types I, II, and III, as well as asymptomatic carriers, relatives of patients, and healthy controls. The study aims to better understand the clinical progression of SMA, including survival, motor function, respiratory and nutritional support, growth, development, and how genetic factors relate to symptoms. Participants include people with SMA types I, II, and III, asymptomatic carriers, relatives of those with SMA, and unrelated healthy individuals. There are no experimental treatments; instead, this observational study follows participants over time to monitor health changes and disease progression. The study began in July 2019 and plans to observe participants for up to 20 years. During the study, researchers collect information on survival time, genetic and symptom correlations, motor abilities, respiratory and feeding support, growth, and development. Regular visits and assessments are conducted to track these factors. The study provides long-term monitoring to gain insights into SMA outcomes and support needs, helping improve understanding for patients and families.