Genetic Disorder

Researchers are studying the smallest effective dose of 131I-apamistamab to prepare patients with advanced sickle cell disease (SCD) for a bone marrow transplant. This is the first time 131I-apamistamab, an investigational drug not yet approved by the FDA, is being used as part of the conditioning regimen before an allogeneic stem cell transplant. The goal is to see if eliminating total body irradiation, which can cause long-term side effects, is possible while still allowing successful transplantation. Participants will receive 131I-apamistamab as an intravenous infusion about ten days before receiving donor stem cells. The dose will be either 100 mCi or 150 mCi based on the dose level. This drug replaces the usual conditioning treatments like chemotherapy, total body irradiation, and Campath antibody. Other treatments involved include sirolimus and Campath, given to support the transplant process. During the study, participants will undergo various assessments including blood tests to monitor graft success, immune recovery, hormone levels, and transplant-related complications up to seven years after transplant. Imaging with planar gamma camera will evaluate drug absorption. Follow-up includes checking for graft failure 42 days post-transplant and monitoring long-term safety. Total participation lasts several years to observe transplant outcomes and side effects.

Researchers are evaluating the efficacy and safety of Apremilast in patients aged 6 years and older with Epidermolysis Bullosa Simplex generalized, a genetic skin condition. This phase 2 open-label study aims to describe how well Apremilast works in reducing symptoms, particularly the occurrence of new blisters, over a 20-week period. Participants will undergo three distinct periods: an initial 8-week treatment phase called challenge, followed by a 4-week period without treatment called dechallenge, and a second 8-week treatment phase called rechallenge. During these periods, patients will take Apremilast and have regular visits to the hospital where doctors will perform study procedures and monitor progress. Throughout the study, participants will have seven visits where doctors will check vital signs, perform clinical examinations, review treatment adherence, and monitor for any side effects. Patients will also complete various questionnaires about their condition. The main measure of success is the efficacy of Apremilast at 20 weeks, along with safety assessments. The total study duration for each participant is 20 weeks.

This research aims to evaluate the treatment of deucravacitinib in adults with inflammatory epidermal genodermatoses, including conditions such as Epidermolysis Bullosa Simplex and various ichthyoses. The study focuses on assessing the efficacy and safety of this treatment for these rare skin disorders. It is a phase 2, open-label trial lasting 44 weeks conducted at a single center. Participants will undergo a treatment schedule divided into three periods: an initial 16-week treatment (challenge period), followed by a 12-week break from treatment (dechallenge period), and a second 16-week treatment period (rechallenge period). During these phases, participants will receive deucravacitinib and be closely monitored. The study uses a challenge-dechallenge-rechallenge design to evaluate treatment effects. Throughout the study, participants will attend eight visits where doctors will check their vital signs, perform clinical exams, and assess treatment adherence and any side effects. Participants will also complete questionnaires and provide blood samples. Researchers will primarily measure the efficacy of deucravacitinib at week 44 and monitor safety. The total participation duration is 44 weeks, ending with a final evaluation.

Researchers are evaluating a 12-week early intervention program designed to address social communication difficulties in young children with developmental disorders. The program targets children diagnosed with conditions such as Autism Spectrum Disorder, neurogenetic disorders, or intellectual disability. The goal is to assess how well this program supports social skills in preschool-aged children. The intervention involves 12 hours per week of intensive treatment delivered either in a center-based preschool setting or at home. Over the 12-week period, children receive structured support tailored to their social communication needs. This program is being studied as a behavioral approach to improve developmental outcomes. Participants will be assessed before and after the 12-week program using parent-rated questionnaires that measure social responsiveness, repetitive behaviors, social dimensions, adaptive behavior, sensory profiles, and self-efficacy. These evaluations help researchers monitor changes in social communication and related behaviors. The total participation duration in the study is 12 weeks, with assessments at the start and end of the program.

Urea cycle disorders (UCD) are rare diseases in China that can cause high mortality and disability, requiring long-term management due to recurring symptoms. This multi-center, prospective, single-arm study aims to evaluate the safety and effectiveness of Glycerol Phenylbutyrate in Chinese children with UCD. The goal is to provide more treatment options and improve clinical care for these patients in China. The study plans a total observation period of five years for patients on long-term treatment with this medication. The study involves 40 children aged from birth to 18 years diagnosed with various types of UCD, including carbamoyl phosphate synthetase I deficiency and others. Participants will receive Glycerol Phenylbutyrate oral liquid, with dosing based on body surface area and divided into multiple daily doses taken with meals. The study includes scheduled clinic visits at 1 month and 3 months after enrollment, followed by visits every 6 months up to 5 years. During these visits, researchers collect data on adverse events, dosage changes, hyperammonemic crises, and blood ammonia levels. Participants will undergo regular assessments including blood tests for ammonia and biochemistry, growth measurements (height, weight, head circumference), and neurocognitive evaluations at specified intervals. The primary outcome is the mean blood ammonia level at 3 months after enrollment. Secondary outcomes include ammonia levels at multiple timepoints, frequency of crises, growth data, dosage adjustments, and various neurodevelopmental scores measured annually. This comprehensive follow-up aims to monitor safety, treatment effects, and overall development throughout the five-year period.

Researchers are exploring and comparing how patients perceive sounds after receiving either cochlear implants or gene therapy for congenital deafness. This study aims to understand differences in speech perception in various environments, music appreciation, and directional hearing between these two treatments. By assessing cognitive and psychological factors alongside auditory development, the study hopes to inform better rehabilitation plans for gene therapy patients. The study includes two groups of congenital deafness patients: those who have cochlear implants and those who have undergone gene therapy for autosomal recessive deafness 9 (DFNB9). Patients receive standard postoperative care and follow-up. The evaluation covers multiple aspects such as speech perception in quiet and noisy settings, cognitive function, psychological status, and auditory cortex growth over time. Participants will be assessed before treatment and at weeks 13, 26, and 52 after intervention. Evaluations include tests of auditory speech perception, cognitive abilities, psychological health, and brain development related to hearing. The study requires participants and their guardians to provide informed consent and cooperate with follow-up visits. Healthy individuals with normal hearing are also included as controls. The goal is to compare outcomes between the two treatments over one year.

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.

MECP2 Duplication Syndrome (MDS) is a rare genetic disorder mostly affecting males, causing severe intellectual disability, motor problems, low muscle tone in infancy, epilepsy, frequent respiratory infections, and often leading to early death before age 25. This condition is caused by extra copies of the MECP2 gene, which is important for brain development and function. Researchers are studying HG204, a new CRISPR RNA-editing therapy designed to reduce the levels of MECP2 protein in the brain and improve symptoms in affected individuals. HG204 uses a special technology called high-fidelity Cas13Y delivered by a single adeno-associated virus vector. The therapy is given as a single injection directly into the brain's ventricles. The study plans to evaluate two dose groups to assess safety and effectiveness. The treatment phase includes a screening period of 8 weeks, followed by the injection visit and a 52-week follow-up to monitor effects and safety. Participants will be closely monitored during this study lasting about 60 weeks, including initial screening, treatment, and follow-up visits. Researchers will track any side effects and changes in clinical status using various developmental and behavioral assessments. Laboratory tests and imaging will be used to evaluate health status, and the primary outcome is the incidence and severity of adverse events over 52 weeks. The study aims to gather detailed information on the safety and potential benefits of HG204 for patients with MDS.

This research aims to observe the effects of Palynziq (pegvaliase) treatment in pregnant women with phenylketonuria (PKU) and on their babies exposed to pegvaliase during pregnancy and breastfeeding. The study is a Phase 4 observational trial that evaluates maternal, fetal, and infant outcomes related to pegvaliase exposure. It includes women diagnosed with PKU who were treated with pegvaliase from two weeks before their last menstrual period (LMP) or at any time during pregnancy. Participants are pregnant women prescribed pegvaliase by their healthcare provider who enroll through a centralized call center. The study collects data retrospectively from at least three months before the LMP, through pregnancy, and during the infant's first year of life. The timing and duration of pegvaliase exposure during pregnancy and breastfeeding, including each trimester, are recorded. Individual participation lasts up to about 21 months. During the study, information will be gathered from the participant's healthcare providers and the infant's doctors. Researchers will monitor pregnancy outcomes and infant development over ten years, focusing on pegvaliase exposure effects. The study also tracks serious adverse events and pegvaliase use during breastfeeding. This long-term monitoring aims to provide detailed data on maternal and infant health following pegvaliase exposure.

This research follows patients with Hemoglobinopathy and Sickle Cell Disease who previously received BEAM-101, a gene-edited cell treatment, in an earlier study. The trial is a long-term observational follow-up to monitor safety and health outcomes over an extended period. It aims to gather important information about the long-term effects and risks after receiving BEAM-101 treatment. Participants in this study have received a single dose of BEAM-101 by intravenous infusion after a conditioning treatment with busulfan. This follow-up study will track their health for 13 years, adding up to 15 years from the initial treatment. Study visits will happen annually for the first 5 years, then every 3 years until year 11, with a final visit at year 15. Additionally, virtual or phone check-ins will occur every 6 months for the first 5 years, then annually thereafter. During the study, participants will undergo regular safety and efficacy assessments to monitor their health, including how well they remain free of severe sickle cell crises and their blood hemoglobin levels. Researchers will review long-term safety data and mortality over the 13 years. The study includes blood tests and other evaluations at scheduled visits and check-ins. Participation will last up to 15 years, with ongoing monitoring to understand the lasting impact of BEAM-101 treatment.