Ornithine Transcarbamylase Deficiency

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 evaluating the safety and pharmacodynamics of multiple doses of ARCT-810, an investigational drug, in adolescents and adults with Ornithine Transcarbamylase (OTC) deficiency. This Phase 2a, open-label study aims to better understand how ARCT-810 works and its safety profile in people aged 12 years and older who have this condition. Participants must have a documented diagnosis of OTC deficiency and be medically managed with a stable diet and supplements. Participants will receive up to five intravenous infusions of ARCT-810 every two weeks, following a diet stabilization period of at least four weeks. The study includes three different dose levels, and dose escalation or cohort expansion may occur after three participants complete each dose level. Participants will continue their usual clinical management for OTC deficiency throughout the study. During the study, participants will have clinic visits at screening and on Days 1, 15, 29, 36, 43, 57, 60, 71, and 85. Researchers will monitor adverse events, pharmacokinetics, fasting plasma ammonia, plasma glutamine, and stable isotope ureagenesis assay values. The primary outcome is the incidence, severity, and dose relationship of adverse events by Day 85. The total participation duration includes ongoing assessments up to Day 85 to evaluate safety and drug effects.

Researchers are collecting both short-term and long-term safety information from adults and children treated for hyperammonemia caused by Methylmalonic Acidemia (MMA) and Propionic Acidemia (PA). This observational study focuses on patients receiving Carbaglu4 as part of their usual medical care, aiming to understand the effects of this treatment in real-world settings. Participants will be treated according to standard medical practices, receiving Carbaglu4 as prescribed by their doctors. The study gathers data on patients treated either as outpatients or inpatients, including details about Carbaglu4 dosing, other treatments for hyperammonemia like diet and protein management, and pregnancy-related outcomes. Data collection continues for about one year after stopping Carbaglu4. During the study, researchers will review plasma ammonia levels and record any adverse events, including their frequency and severity. They will also collect information on pregnancy outcomes and effects on infants up to one year old. No additional treatments or interventions are administered beyond routine care. This allows for monitoring safety and developmental outcomes over time in this patient group.

Ornithine Transcarbamylase (OTC) deficiency is a genetic metabolic disorder affecting the liver's ability to detoxify ammonia, often causing severe neurological damage, coma, or death shortly after birth. This condition is more common and severe in male babies. Researchers are studying ECUR-506, an investigational gene editing therapy, to evaluate its safety, tolerability, and effectiveness in treating male infants under 9 months old with neonatal-onset OTC deficiency in a Phase 1/2/3 open-label trial. ECUR-506 delivers a functional OTC gene and a gene for an editing enzyme using a viral vector through a single intravenous infusion. The study tests three dose levels: low, intermediate, and high, each given once by IV infusion. Participants receive only one dose and are monitored over time to assess the impact of this gene editing treatment on their condition. During the study, babies will be closely monitored for safety and response through physical exams, neurologic assessments, vital signs, blood tests, urinalysis, and ECGs at scheduled times up to 24 weeks after infusion. Researchers will track adverse events, ammonia levels, hospitalizations, and other clinical outcomes such as survival and need for liver transplant. The total participation period covers about 24 weeks of follow-up to evaluate ECUR-506's effects and safety.

Researchers are investigating whether people with certain inherited ammonia metabolism disorders can successfully measure their ammonia levels daily at home. The study focuses on understanding participants' ability to regularly use a new ammonia measurement device and complete daily health monitoring. This research aims to improve management of conditions like urea cycle disorders and other metabolic diseases that affect ammonia processing in the body. Participants will use an investigational ammonia device that measures total ammonia from a single drop of blood using a reusable instrument and single-use cartridge. They will be asked to measure their ammonia levels daily, along with temperature, heart rate, and blood oxygen. The study includes two in-person clinic visits and an optional extension period, with monitoring lasting approximately 240 days, extendable by another 120 days. During the study, participants will complete daily surveys and record their health measurements to help researchers track adherence and gather data. The main outcome measured is the percentage of daily ammonia tests completed. Researchers will also analyze descriptive statistics and correlations over the study period to better understand home monitoring feasibility and patterns. Participants' involvement lasts around 8 months, with optional continued participation for an additional 4 months.

Ornithine transcarbamylase deficiency (OTCD) is a rare inherited liver disorder that prevents the body from maintaining normal ammonia levels, leading to dangerous ammonia buildup in the blood. This condition can cause life-threatening episodes called hyperammonaemic decompensations, which may result in vomiting, movement problems, lethargy, coma, and impaired neurological development in children. Current treatments include drugs to reduce ammonia and low-protein diets, but these do not always prevent these dangerous episodes. Liver transplantation can be life-saving but may be delayed, risking further neurological harm. The trial is testing a gene therapy called AAVLK03hOTC, designed to target the liver and enable production of the missing OTC enzyme. The study involves escalating doses given by intravenous infusion in children from birth to 16 years old, with groups receiving low to high doses and an additional group receiving the dose with the best safety and efficacy balance. This gene therapy aims to help the liver function normally, reduce dangerous ammonia buildups, and act as a bridge to liver transplant. Participants will be closely monitored for safety and effectiveness for at least 12 months after infusion, including tracking any adverse events. Long-term follow-up of up to four years will assess ongoing safety. Researchers will regularly assess ammonia levels, liver function, and overall health to understand the gene therapy's impact on managing OTCD. The study is open-label and involves multiple centers, aiming to provide important information on this new treatment option for children with OTCD.

Urea cycle disorders (UCDs) are common inherited liver metabolism conditions. Improved diagnosis and treatments have increased survival rates, revealing some long-term liver complications like dysfunction and fibrosis in some patients. These liver issues vary depending on the specific metabolic defect causing the disorder. The study aims to better understand these complications by examining liver tissue samples from individuals diagnosed with any UCD. This research involves reviewing past medical records and prospectively collecting liver tissue samples from patients with confirmed UCD diagnoses. It includes individuals who have had or are planning to have liver biopsies or transplants. This observational study is conducted across multiple centers within the Urea Cycle Disorders Consortium, including Baylor College of Medicine and Children’s National Medical Center. Participants' liver samples will be evaluated for fibrosis, fat accumulation (steatosis), and glycogen buildup (hepatic glycogenosis). Researchers will analyze histopathology reports, biopsy slides, and tissue blocks to identify these outcomes. The study collects data retrospectively and prospectively, tracking histological changes to better understand liver complications in UCD. Participation involves no interventions and focuses on reviewing existing and new liver tissue findings until study completion in June 2026.

Researchers are conducting a long-term follow-up study lasting 14.5 years to assess the safety and lasting effects of an investigational product (IP) used in previous iECURE studies. The study also aims to gather ongoing natural disease information from participants who enrolled but were not treated with the IP. Participants continue their usual medical care prescribed by their doctors throughout the study. This observational study does not provide any investigational treatment. Instead, it follows two groups: those who received the IP in earlier iECURE studies and those who were enrolled but not dosed. No new drug or therapy is given as part of this follow-up. Participants maintain their prescribed standard care while researchers collect data over time. Participants will be monitored regularly for safety, growth changes, and other health measures over 14.5 years. The study collects information on adverse events, changes in height and weight, urinalysis results, and detailed laboratory tests including vector clearance in blood, saliva, urine, and feces. Researchers also track serious health events related to the disease, hospitalizations, and survival outcomes. This comprehensive follow-up aims to provide valuable long-term data on participants' health and treatment effects.

Urea cycle disorders (UCD) are rare inherited conditions that affect how the body processes protein, leading to dangerous ammonia buildup that can cause brain damage or death. This research aims to study a large group of individuals with different types of UCD to understand the natural course of the disease, how it progresses, treatments used, and patient outcomes over time. The study is observational and focuses on tracking biochemical status, growth, cognitive function, and treatment effects in participants. Participants will have an initial visit that includes medical and diet history, physical and neurological exams, psychological testing, and blood tests. Those with neonatal onset UCD will be assessed every 3 months until age 2, then every 6 months after that. Participants with late onset UCD will have evaluations every 6 months. Psychological testing occurs every 2 years and can last from 30 minutes to 3 hours depending on the tests. During the study, participants will undergo regular assessments lasting 2 to 3 hours at each visit. Researchers will monitor disease severity through various biomarkers and clinical indicators, evaluating the safety and effects of different treatments like alternate pathway therapy and transplantation. The study will continue longitudinally, allowing for long-term observation of participants' health and cognitive outcomes as they grow and receive care.

Urea cycle disorders (UCDs) are rare genetic conditions affecting how the body removes ammonia, a waste from protein breakdown. This research focuses on ornithine transcarbamylase deficiency (OTCD), the most common type, and other related disorders such as argininosuccinate synthetase deficiency (ASSD) and argininosuccinate lyase deficiency (ASLD). The study aims to understand brain changes and cognitive effects linked to these disorders by comparing brain chemical levels and structural abnormalities using advanced imaging and neuropsychological testing. The study includes three parts: a longitudinal study of OTCD, a recovery study after hyperammonemic episodes, and a longitudinal study of distal UCDs like ASSD and ASLD. Participants will undergo various brain imaging methods including standard MRI, functional MRI, diffusion tensor imaging, and magnetic resonance spectroscopy to assess brain chemistry and structure. Behavioral and cognitive tests will be performed alongside imaging during initial and follow-up visits. Participants will attend initial visits involving medical history reviews, neurological exams, and cognitive and motor testing over one to two days. They will undergo multiple imaging sessions while performing tasks during functional MRI. Researchers will measure changes in brain glutamine and myo-inositol levels and fractional anisotropy over two years, alongside behavioral outcomes. The study includes safety monitoring and aims to clarify brain damage progression in different UCD types.