Phelan-McDermid Syndrome

Researchers are evaluating the effectiveness and safety of NNZ-2591 compared to a placebo in children aged 3 to 12 years with Phelan-McDermid Syndrome, a rare genetic condition caused by abnormalities in the SHANK3 gene. This Phase 3, randomized, double-blind, placebo-controlled study includes multiple centers to ensure broad participation and reliable results. After informed consent, participants will enter a 4-week screening period to confirm eligibility and assess baseline symptoms. Those who qualify will be randomly assigned to receive either NNZ-2591 or a matching placebo, both taken orally twice daily, during a 13-week treatment period. Following treatment, there will be a 2-week safety follow-up to monitor participants. During the study, children will undergo various assessments including the Phelan-McDermid Syndrome Assessment of Change and the Vineland Adaptive Behavior Scales to evaluate communication and behavior changes. Caregivers will provide impressions of change, and researchers will monitor safety through clinical evaluations. The total participation time per child is approximately 17 to 19 weeks.

Researchers are evaluating the long-term safety, tolerability, and effectiveness of NNZ-2591 in children with Phelan-McDermid Syndrome in this Phase 3, open-label extension, multicenter study. This study focuses on pediatric participants who have previously taken part in related NNZ-2591 studies. The aim is to better understand how this oral medication works over an extended period in this specific group. Participants who qualify will receive NNZ-2591 orally twice daily for 52 weeks during the Treatment Period. This is followed by a 2-week Safety Follow-Up to monitor any effects after treatment ends. The total time each participant spends in the study is up to 56 weeks, allowing researchers to observe the medication's impact over nearly a year. During the study, children will undergo various assessments including symptom severity checks and baseline characteristics before starting treatment. Researchers will monitor safety through adverse event tracking, physical exams, laboratory tests, and heart monitoring with ECGs. Effectiveness will be measured using several scales designed to assess changes in symptoms and behavior over months 3 and 12. Participants' health and responses will be closely followed throughout the study and safety follow-up period.

Researchers are evaluating the safety, tolerability, and clinical effects of a gene therapy called JAG201 in children and adults who have SHANK3 haploinsufficiency caused by certain genetic mutations or deletions. This early phase 1/2 study focuses on pediatric participants first and aims to gather initial data on how this treatment works and its potential effects. The study is open-label and involves a single dose of gene therapy delivered directly into the brain's ventricles. Participants will receive one dose of JAG201 through intracerebroventricular injection on Day 1 after eligibility screening. The study includes two pediatric groups receiving different doses, with a total target of six children aged 2 to 9 years. Following treatment, participants stay in the hospital for close monitoring. The study consists of several phases: pre-screening and screening, administration and perioperative care, initial follow-up up to two years, and long-term follow-up lasting five years. During the study, participants will have regular visits to assess safety, clinical responses, and any side effects. Researchers will monitor for adverse events, laboratory abnormalities, and immune responses over five years. They will also assess changes in developmental and cognitive measures using specific tests. This long-term monitoring ensures careful observation of the gene therapy's effects and participant well-being throughout the study period.

Researchers are evaluating the safety, tolerability, and early effects of RB001, a gene therapy, in children with SHANK3-related Phelan-McDermid Syndrome (PMS), a rare neurodevelopmental disorder caused by genetic deletions or mutations affecting brain development. This condition leads to intellectual disability, severe language delays, autism-like behaviors, and other symptoms. The study aims to gather initial clinical data on a single dose of RB001 delivered directly into the brain's ventricles. The treatment involves a single intracerebroventricular injection of RB001, which uses a viral vector to deliver a corrected SHANK3 gene. The study plans to enroll about eight pediatric participants aged 3 to 18 years. Each participant will be involved in a 14-month study period including a 2-month screening, a 7-day hospital stay around the time of the injection, and a 12-month follow-up outpatient period to monitor effects and safety. Participants will undergo various assessments including clinical evaluations of autism severity, developmental scales, intelligence tests, and behavioral checklists over 52 weeks following treatment. Researchers will also monitor immune responses, viral presence in the body, and overall safety. The trial's goal is to assess how well patients tolerate the treatment and to observe any early signs of benefit or risks over one year after the injection.

Researchers are investigating how brain development in infants up to 6 years old relates to their social emotions and communication skills. The study also examines the influence of genetic factors and maternal exposures during pregnancy, such as environmental factors and maternal inflammatory conditions. The goal is to provide a foundation for targeted interventions to improve infants' social and emotional abilities and overall brain development. The study uses advanced brain imaging techniques, including functional magnetic resonance imaging (fMRI) with multiple methods like blood-oxygen-level dependent imaging and perfusion weighted imaging. These imaging methods, combined with cloud-based analysis and artificial intelligence, help map brain structure, function, connectivity, and development trajectories. Researchers also assess children's social-emotional behavior using the Chinese Urban Children's Emotion and Social Assessment Scale and neurological development with the Gesell Developmental Scale. Blood samples are collected for genetic and biomarker analysis, and family and maternal health information during pregnancy is gathered through questionnaires and clinical history. Participants will undergo brain scans and assessments at the start of the study and again six months later, with intelligence quotient measured annually from ages 3 to 6. Researchers will monitor changes in brain structure, function, blood flow, EEG, social-emotional behavior, brain development, and child mental health. Biomarker screening occurs once at baseline. The study spans from infancy through early childhood, with data collected to understand brain development changes and predict developmental outcomes over time.

Researchers are evaluating an adapted telehealth functional behavioral therapy called FBTsIDD, designed to promote appropriate communication and behavior in children with syndromic intellectual and developmental disorders. The study focuses on improving behavioral strategies for these individuals, assessing how well this approach works for youth aged 2 to 12 years with genetic syndromes and developmental delays. Participants will receive weekly or biweekly virtual therapy sessions with a study therapist. The therapy includes functional behavioral training steps such as screening, preference assessment, functional analysis, and tailored interventions like Functional Communication Training or Competing Stimulus Treatment depending on behavior type. The study compares this approach to positive parenting strategies as usual treatment. During the study, participants will complete virtual assessments at intake and monthly for 3 to 6 months. Researchers will monitor behavior changes using tools like the Clinical Global Impression and Parent Target Problems Inventory. Adverse events will be tracked monthly. The total study participation lasts up to six months with regular virtual visits and evaluations to assess therapy impact and safety.