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: UBE3A gene deletion, uniparental disomy, or imprinting center defect. The study is a Phase 1/2 trial designed to assess how well this gene replacement therapy works and its tolerability in these participants. Angelman syndrome is a genetic condition caused by problems with the UBE3A gene, and MVX-220 aims to provide a functional copy of this gene. Participants receive a single dose of MVX-220 through an injection into the cisterna magna, a fluid space near the brain. The study includes two main groups: adults aged 18 to 50 years and children aged 4 to 8 years. There is also an optional third group that may include both adults and children aged 4 to 50 years. Before and briefly during the study, participants take steroids to reduce immune reactions to the gene therapy. An independent board reviews safety data after adults are treated before children enroll. Throughout the study, participants are monitored for safety and treatment effects for two years after receiving the gene therapy, followed by a longer, less frequent follow-up period lasting three more years, totaling five years of observation. Researchers assess adverse events and measure changes in communication, development, behavior, mobility, sleep, quality of life, viral DNA levels, and brain activity using various scales, wearable devices, diaries, and EEG tests. Regular clinical exams, lab tests, and vital sign checks are also performed to track safety.

Researchers are evaluating the safety and effectiveness of GTX-102 in individuals with Angelman syndrome, a genetic condition. This study includes participants of different ages and genetic types of Angelman syndrome. It is a phase 2, open-label basket study with several subprotocols designed to assess the treatment across various groups and age ranges, sponsored by Ultragenyx Pharmaceutical Inc. Participants receive GTX-102, an antisense oligonucleotide, administered through intrathecal (spinal) injections. Dosing starts with increasing amounts until the target dose is reached, followed by maintenance doses every three months. The study includes subprotocols A, B, C, and D; some groups receive treatment directly, while one group initially receives no treatment before starting GTX-102. After completing the study, participants may continue treatment in a long-term extension. During the study, participants undergo screening, treatment, and follow-up visits with assessments including cognitive, communication, motor skills, behavior, and sleep evaluations. Safety is closely monitored by tracking adverse events and lab tests. Measurements are taken at baseline and after about 11 months. The study lasts until 2030, with ongoing evaluation of participant response and safety throughout the treatment and follow-up periods.

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 Children's Hospital and will continue through April 2031. The collected data aims to support future research and enhance understanding of Angelman syndrome's 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.

Myelodysplastic syndromes (MDS) are chronic blood disorders marked by ineffective blood cell production and normal marrow richness. This research aims to understand the biological and clinical aspects of MDS, including its progression to acute leukemia, which occurs in 30 to 40% of cases. The study focuses on the genetic and molecular diversity of MDS and seeks to identify markers predicting disease progression through a biocollection. The study involves collecting and analyzing biological material from patients diagnosed or suspected of having MDS. It explores three key scientific projects: splicing abnormalities related to SF3B1 mutations, the role of chromosomal deletions such as 5q affecting splicing genes RBM22 and SLU7, and the progression of MDS to acute myeloid leukemia by studying the clonal architecture of malignant cells. These projects use advanced genetic and molecular analysis techniques to deepen understanding of MDS mechanisms. Participants provide biological samples and clinical data, which are used for detailed genetic and functional studies. The study monitors patients over time to observe disease evolution and identify prognostic markers. The primary outcome is an epidemiologic study of the MDS patient cohort over five years. Participation includes consenting to data and sample collection, enabling researchers to analyze molecular changes and better understand MDS progression and prognosis.

Researchers are investigating bladder and bowel functions, participation levels, and quality of life in children with intellectual disabilities aged 5 to 12 years. This study addresses a gap in research by examining these factors together in children with intellectual disability, including those attending Special Education and Rehabilitation Centers, compared to typically developing children. Intellectual disability and related neurodevelopmental and psychiatric conditions often impact bowel or bladder dysfunction, which in turn affects daily life and well-being. The study includes two groups: children with mild to severe intellectual disabilities and typically developing children, both aged 5 to 12. Assessments will use questionnaires such as the Childhood Bladder and Bowel Dysfunction Questionnaire, Dysfunctional Voiding and Incontinence Scoring System, and the Lower Urinary Tract Symptom Score to evaluate bladder and bowel function. Child participation will be measured with the Child and Adolescent Scale of Participation, while parental quality of life and children's quality of life related to gastrointestinal symptoms will be assessed using the Nottingham Health Profile and Pediatric Quality of Life Inventory - Gastrointestinal Symptoms Module, respectively. Participants and their parents will provide sociodemographic information including age, height, weight, marital status, and education level. The study involves baseline evaluations using various symptom and participation scales to measure bladder and bowel function and quality of life. This cross-sectional observational study started in September 2025 and will conclude in December 2026. It aims to better understand the challenges faced by children with intellectual disabilities and their families, providing important insights into their health and daily functioning.

Researchers are studying how people with intellectual disability (ID) respond to unpleasant sensations compared to those without ID. The goal is to understand brain activity and pain perception in individuals aged 8 to 30 years with ID versus healthy volunteers. This research addresses the gap in knowledge about pain experiences in people with ID, who often have additional physical disabilities affecting their nerves, bones, muscles, and gastrointestinal systems. The study involves a special device called the TSA2 Thermosensory Stimulator to provide heat, cold, brushing, and mild electrical stimuli to various body parts. Brain responses will be measured using electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Participants will wear a sensor cap and have sensors placed on their chest, fingers, and around their body to monitor heart rate, breathing, sweat, and brain activity during the stimuli. There are two groups: individuals with intellectual disability and healthy controls. Participants will attend one visit lasting up to four hours, though those with ID may have up to five shorter visits. They will undergo tests to assess intellectual disability level, physical exams, and answer questions about pain, sensory responses, and social behavior. Caregivers may assist if needed. The study will measure brain activation, physiological responses like heart rate and skin conductance, and behavioral reactions to stimuli. The primary outcome is to provide a quantitative measure of pain perception by the study's end.

Researchers are evaluating the safety, tolerability, and early effects of a single intrathecal injection of a dual vector AAV-CHD3-R1025W base editor in children aged 2 to 10 years with developmental disorders caused by the R1025W mutation in the CHD3 gene. This early phase 1 study focuses on developmental delay disorder, intellectual disability, and rare diseases linked to this specific genetic mutation. The treatment involves delivering the base editor using a dual vector adeno-associated virus (AAV) system through an intrathecal injection, which introduces the gene-editing therapy directly into the spinal fluid. During treatment, children's vital signs are closely monitored to detect any immediate adverse effects. After the injection, participants are followed regularly to track the success of gene editing and observe any improvements in neurodevelopment. Long-term safety is also assessed through ongoing monitoring of possible adverse events. Participants will undergo assessments over a 26-week period to measure safety and preliminary efficacy. The main outcome is the incidence of serious adverse events related to the treatment within this timeframe. Additional evaluations include changes in clinical global impression scales and patient global impressions of improvement. The study involves close monitoring of vital signs, immune function, and neurodevelopmental progress to ensure thorough evaluation throughout the trial period.