Angelman Syndrome

Adults with intellectual disabilities often face challenges in social situations due to difficulties in processing social information, especially in recognizing facial emotions. This research evaluates a cognitive remediation program called Re9habilitus, designed to improve attentional and visuospatial functions to reduce behavioral disorders in adults with intellectual disabilities who do not have autism spectrum disorder. The study aims to validate whether this program can help address specific cognitive and behavioral issues in daily life for this population. Participants are randomly assigned to either the Re9habilitus cognitive remediation program, which focuses on improving attention and spatial perception related to social behavior, or to a control group engaging in manual activities and computer-based research tasks. The study compares these two approaches to assess their effects on behavioral disorders and cognitive functions. During the study, participants are assessed on changes in hyperactivity and non-compliance behaviors using the Aberrant Behavior Checklist scale over six months. Researchers also measure improvements in facial emotion recognition and attentional functions at the start, end, and six months after the intervention. The total participation time and safety monitoring details are aligned with the evaluation periods, ensuring thorough follow-up to observe lasting effects.

Researchers are conducting an observational study to understand how Angelman syndrome AS progresses naturally in children and adults who have a confirmed genetic diagnosis. The study focuses on changes in developmental skills like communication, motor abilities, and adaptive behaviors over one year. It also explores specific brain activity and sleep patterns that may be linked to changes in AS symptoms. This study aims to gather important data that can help improve future clinical trials and develop better diagnostic tools and treatments for AS. Participants will attend up to five visits over 12 months, approximately every three months, where they will undergo various assessments. These include standardized tests and questionnaires about their development, behaviors, and sleep, with caregiver assistance. Participants will have electroencephalograms EEGs to record brain activity and wear a sleep-monitoring device at home to collect actigraphy data. The study includes three cohorts based on age children and adolescents aged 1 to 17, a focused group of children aged 1 to 12, and a small adult group aged 18 and older. Throughout the study, participants will complete developmental and behavioral assessments at baseline and every three months to measure changes in cognitive, communication, motor, and adaptive behavior skills. Researchers will also track common co-occurring conditions such as epilepsy and sleep problems. Data from EEGs, actigraphy, and questionnaires will be analyzed to understand age-related changes and symptom patterns. The total participation time is one year, with regular monitoring and evaluations to capture the natural history of AS.

Researchers are evaluating the safety and effectiveness of MVX-220 gene therapy in children and adults with Angelman syndrome who have specific genetic types including UBE3A gene deletion, uniparental disomy, or imprinting center defects. This phase 12 study aims to understand how well this gene replacement therapy works and its safety profile in these participants. The trial is sponsored by MavriX Bio, LLC and involves a single group of participants without a control group. Participants will receive a single dose of MVX-220 administered by injection into the cisterna magna. The study includes two primary groups adults aged 18 to 50 years and children aged 4 to 8 years. There is also an optional third group that may include adults and children aged 4 to 50 years. All participants will take steroids before and briefly during the study to help reduce immune responses related to the gene therapy. Safety data from adults will be reviewed before enrolling children. Participants will be monitored closely for safety and effectiveness for two years after treatment, with assessments including physical exams, laboratory tests, ECGs, and questionnaires measuring communication, development, behavior, sleep, and quality of life. After the initial period, monitoring will continue less frequently for an additional three years, totaling five years of follow-up. Researchers will also measure viral DNA levels and EEG parameters to assess treatment impact and safety throughout the study.

Researchers are evaluating the safety and effectiveness of GTX-102 in people with Angelman syndrome, a genetic condition, across different ages and genetic types. This Phase 2 open-label basket study includes subprotocols A, B, C, and D, each following a similar design with Screening, Loading, and Maintenance periods. Some subprotocols involve randomization, and participants can continue treatment in a long-term extension after completing the study. Participants receive GTX-102 via intrathecal injections every three months. Dosing starts at a lower level and increases until a target dose is reached. Different subprotocols include groups based on age and Angelman syndrome genotype, with some receiving no treatment initially before starting GTX-102. The study evaluates treatment effects in groups ranging from children as young as 1 year old to adults up to 65 years old. Throughout the study, participants undergo scheduled visits with assessments including cognitive and motor function tests, behavior rating scales, and safety monitoring for adverse events. Researchers collect data up to about 17 months from baseline, with monitoring of treatment-emergent and serious adverse events. Participants also have imaging and lab tests like lumbar punctures and blood work. After the initial study, participants may opt to continue in a long-term extension to further assess GTX-102s effects and safety.

Researchers are conducting a prospective, longitudinal natural history study to better understand Angelman syndrome in children and adults. The study aims to collect detailed data through both investigator observations and reports from parents. This information will help establish Angelman syndrome-specific norms for outcome measures, supporting the design of future clinical trials and improving care for those affected by the condition. This observational study does not involve any treatments or interventions. Instead, participants will be followed over time to gather information about their medical history and development. The study collects data through various assessments including the Vineland Adaptive Behavior Scales, Bayley Scales of Infant and Toddler Development, and the Observer-Reported Communication Ability Measure, conducted over an average period of one year. Participants will be involved in regular evaluations that include medical history reviews and developmental assessments. These assessments provide valuable information on communication abilities and adaptive behaviors. The study is sponsored by Boston Childrens Hospital and will continue through April 2031. The collected data aims to support future research and enhance understanding of Angelman syndromes progression and care needs.

Cerebral palsy CP is a condition caused by brain injury in babies that affects movement and muscle tone. Some children with CP may have other developmental challenges like learning difficulties, but many have mostly motor skill issues. This study aims to reduce the age at which CP is diagnosed by using new and specific assessments in high-risk infants, such as those born prematurely or with brain injuries. It also seeks to better predict which children might need support for learning, language, or other developmental outcomes. The research is coordinated by University College Cork and supported by Research Ireland and the Cerebral Palsy Foundation, USA. The study compares two groups a high-risk group of infants with factors like prematurity or hypoxic-ischaemic encephalopathy, and a control group of healthy term infants who did not require neonatal intensive care. Participants will be assessed in outpatient clinics using novel examinations to track their development. The study will take place at multiple hospitals in Ireland and will monitor infants from near term up to 24 months corrected gestational age. During the study, infants will have regular assessments at various time points, including near term to 4 months corrected gestational age, birth to 6 weeks, and 4 to 24 months. Researchers will evaluate motor and intellectual outcomes over a five-year period with follow-ups at 4 and 18 months. Guardians will provide consent and comply with study requirements, and the team will observe the infants progress to better understand early signs of CP and developmental impairments.

Researchers are evaluating the safety and effectiveness of intrathecal rugonersen in children and adults with Angelman syndrome. This Phase III study compares rugonersen to a sham procedure in up to 165 participants to assess improvements in cognition and communication. Following this, there is an open-label extension lasting about 116 weeks to monitor long-term effects and safety of the treatment. Participants will be randomly assigned to receive either the study drug rugonersen or a sham procedure administered intrathecally. The initial treatment phase lasts 56 weeks, after which participants may join the open-label extension for up to 2 years to continue receiving and being assessed for the investigational treatment. Both parts include multiple clinical visits and monitoring procedures. During the study, participants will undergo assessments including cognitive and communication testing, clinician evaluations of Angelman syndrome symptoms, EEG recordings, and safety monitoring for adverse events. Blood draws, lumbar punctures, and intrathecal injections will be performed under sedation or anesthesia as needed. Caregivers play an important role in providing information and completing assessments. The total participation duration can extend over several years including long-term follow-up.

Myelodysplastic syndromes MDS are chronic blood disorders marked by ineffective blood cell production and normal marrow richness. MDS affects mostly older adults and carries a risk of progressing to acute leukemia in 30 to 40% of cases. This study aims to build a biocollection to better understand the clinical and biological markers that predict progression to acute myeloid leukemia by studying subgroups of MDS patients with different genetic and chromosomal characteristics. The study involves collecting biological samples and clinical data from patients diagnosed with or suspected of having MDS. Researchers will investigate specific genetic mutations affecting RNA splicing, particularly mutations in the SF3B1 gene, and chromosomal deletions such as 5q deletion. The study focuses on three scientific projects exploring splicing abnormalities, the impact of chromosomal deletions on disease progression, and the clonal architecture in patients progressing to leukemia. Participants will provide biological material collected at the research center, and clinical data will be gathered during diagnosis and follow-up visits. The research team will perform detailed molecular analyses, including RNA sequencing, protein detection, and enzymatic studies to understand the disease mechanisms. The primary outcome is an epidemiologic study of the MDS cohort over five years, aiming to identify prognostic markers and improve understanding of MDS progression. Participation may last several years, with ongoing data and sample collection.

Researchers are conducting a study to understand bladder and bowel functions, participation, and quality of life in children aged 5 to 12 years with intellectual disabilities compared to typically developing children. This condition involves a range of urinary and bowel symptoms that often affect children with developmental challenges, impacting their daily life and well-being. The study aims to fill a gap in knowledge by evaluating these functions together along with child participation and parental quality of life. The study involves two groups children diagnosed with mild to severe intellectual disabilities and typically developing children within the same age range. Data will be collected through questionnaires assessing bladder and bowel dysfunction, child participation, and quality of life for both children and their parents. The study will be conducted as a cross-sectional observational assessment without any intervention. Participants will provide sociodemographic information and complete various validated questionnaires including the Childhood Bladder and Bowel Dysfunction Questionnaire, Dysfunctional Voiding and Incontinence Scoring System, and Pediatric Quality of Life Inventory. Parental quality of life will also be assessed. The study will help researchers understand how bladder and bowel issues affect participation and quality of life in these children. The total study duration extends until December 2026, with assessments occurring at baseline.

Researchers are studying how people with intellectual disability ID respond to unpleasant sensations compared to those without ID. The study aims to better understand brain activity and pain perception in individuals aged 8 to 30 years. This is important because people with ID often have physical disabilities that can cause pain, but little research has focused on their experience of pain. Participants will undergo tests measuring brain activity using devices like EEG and functional near-infrared spectroscopy. They will experience different stimuli such as heat, cold, brushing, and mild electrical sensations applied to their body. The study compares brain responses and physiological reactions like heart rate and skin conductance between individuals with ID and healthy controls. The devices include a thermal stimulator to deliver these sensations, and measurements will be taken from sensors placed on the head, chest, fingers, and breathing. Participants will have one visit lasting up to four hours, or those with ID may attend up to five shorter visits. They will complete assessments including physical exams, questionnaires about pain and sensory responses, and social behavior. Caregivers may assist with answering questions if needed. Researchers will measure brain activation, physiological signals, and behavioral responses to understand pain perception. This study aims to provide objective measures of pain in people with ID and healthy volunteers.