Phelan-McDermid Syndrome

Researchers are evaluating the efficacy and safety of NNZ-2591 compared to a placebo in children aged 3 to 12 years with Phelan-McDermid Syndrome, a genetic condition caused by an abnormality of the SHANK3 gene. This Phase 3, randomized, double-blind, placebo-controlled study aims to assess how NNZ-2591 affects symptoms and adaptive behaviors in pediatric participants. Participants first enter a 4-week screening period to confirm eligibility and assess symptom severity. Those eligible are randomly assigned to receive either NNZ-2591 or a matching placebo, both administered orally twice daily, over a 13-week treatment period. After treatment, there is a 2-week safety follow-up to monitor participants. During the study, participants undergo various assessments including the Phelan-McDermid Syndrome Assessment of Change PMSA-C and the Vineland Adaptive Behavior Scales-3 to measure communication and behavior changes. Caregiver impressions and clinical ratings are also collected. The total time commitment for participants is about 17 to 19 weeks, including screening, treatment, and follow-up periods.

This research aims to evaluate the long-term safety, tolerability, and effectiveness of NNZ-2591 in children with Phelan-McDermid Syndrome. It is a Phase 3, open-label extension study involving pediatric participants who have previously taken part in related studies. The study focuses on assessing how NNZ-2591 affects symptom severity and overall health over an extended period. Participants will receive NNZ-2591 orally twice daily during a 52-week treatment period. Before starting treatment, eligibility will be confirmed through assessments including baseline characteristics and symptom severity. After completing the treatment phase, participants will enter a 2-week safety follow-up to monitor any ongoing effects or side effects. Throughout the study, participants will undergo various evaluations including clinical assessments, ECG monitoring, laboratory tests, and symptom severity scales. Safety and tolerability will be measured by tracking adverse events, vital signs, and laboratory results. Efficacy will be assessed using standardized tools such as the Phelan-McDermid Syndrome Assessment of Change and Vineland Adaptive Behavior Scales. Overall participation may last up to 56 weeks.

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 12 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 brains 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 therapys effects and participant well-being throughout the study period.

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 childrens social-emotional behavior using the Chinese Urban Childrens 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.