Active clinical trials for "Homocystinuria"

Homocystinuria caused by Cystathionine Beta-Synthase (CBS) Deficiency is a rare autosomal-recessive metabolic condition characterized by an excess of homocysteine (Hcy) in the plasma, tissues and urine. It is due to reduced or absent activity of the CBS enzyme, and is also known as classical homocystinuria. The symptoms associated with homocystinuria are variable in severity and time of onset across patients. Some affected individuals may have mild signs of the disorder; others may have multi-systemic involvement including potentially life-threatening complications. Homocystinuria can affect many different organ systems of the body; the four most commonly involved are the eyes, central nervous system, skeleton, and the vascular system. The current approaches to treatment of homocystinuria patients include a highly restrictive diet and use of dietary supplements. Lifetime compliance with this diet is poor. Pegtibatinase (TVT-058) represents a novel therapeutic approach that incorporates the use of a modified version of the native, human CBS (hCBS) enzyme. The goal of treatment is to introduce the CBS enzyme into circulation, resulting in reduced Hcy levels, increased cystathionine (Cth) and cysteine (Cys) levels.

A prospective, open label, acceptability study to evaluate PKU, MSUD, HCU, TYR and GA express plus in the dietary management of 40 patients with IEM. The following parameters will be assessed: adherence to prescribed dietary intakes, palatability, usability, gastrointestinal tolerance, clinically relevant routine biochemical parameters, timeframe to transition and contribution of the express plus range to overall protein substitute intake over a 28 day period.

Newborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life. Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents.

The purpose of the study is to characterize the clinical course of homocystinuria in pediatric and adult patients aged 1 to 65 years under current clinical management practices

Inborn errors of metabolism (IEM) are not have specific clinical signs, they masquerade as other diseases, and are difficult to diagnose using only clinical manifestations or routine laboratory tests. IEM most commonly manifest in early infancy and childhood. Despite the fact that most IEM are rare in the population, they occupy one of the first places in the structure of childhood pathology, early infant mortality and disability. IEM often remains undiagnosed, while timely diagnosis and timely treatment started can prevent severe systemic damage leading to death and disability. The appointment of a special treatment (diet therapy, cofactors, enzyme replacement therapy) prevents or significantly inhibits the development of the pathological process, especially if the diagnosis is made in the early stages of the disease. To start pathogenetic treatment as early as possible, it is necessary to diagnose IEM as accurately and as early as possible. Among the diseases included in mass screening programs IEM are especially important due to the development of disability and early mortality in the absence of timely diagnosis and treatment, as well as a high risk of recurrence in burdened families. In this connection, the main goals of mass screening - the prevention of disability in children and the reduction of early infant mortality - dictate the need to introduce modern technologies for preclinical diagnosis of IEM. Based on the results of the study, it is planned to scientifically substantiate the need for the introduction of selective screening of children for hereditary metabolic diseases using the technology of tandem mass spectrometry in the Republic of Kazakhstan for timely diagnosis, therapy of IEM and prevention of disability. The introduction of a selective newborn screening program for IEM should always be preceded by a study aimed at studying the prevalence of the disease in a certain region, determining regional reference values of the studied metabolites. Local incidence and outcome data can be used to persuade health officials to prioritize screening in health care spending. The main scientific question and hypothesis of the project is whether it is necessary to introduce tandem mass spectrometry technology in the neonatal screening program for IEM.

The purpose of this study is to evaluate the safety and tolerability of pegtarviliase in approximately 36 subjects with homocystinuria due to CBS deficiency.

In homocystinuria due to cystathionine beta synthase (CBS) deficiency or classical homocystinuria, decreased blood cysteine levels are observed. Cysteine is essential for the synthesis of molecules such as glutathione and taurine. Main functions of glutathione are to detoxify drugs and to scavenge reactive oxygen species. N-acetylcysteine is a commercially available drug chemically similar to cysteine. In CBS deficient animal models, N-acetylcysteine supplementation improves cysteine and liver glutathione concentrations. N-acetylcysteine also acts directly as a scavenger of free radicals. In CBS deficiency, increased oxidative damage has been described and possibly contributes to the clinical manifestations of CBS deficiency. Acetaminophen (Paracetamol) is a common painkiller and its overdose (>4 g/day) is a major cause of acute liver failure. Glutathione is required for Acetaminophen detoxification, and the preferred treatment for an overdose is the administration of N-acetylcysteine. The aim of this study is to demonstrate that CBS deficiency patients have glutathione depletion and to investigate if Acetaminophen can induce subclinical liver damage and if N-acetylcysteine supplementation could prevent the toxic-effects of acetaminophen. The investigators' hypothesis is that CBS deficiency patients have an inadequate supply of cysteine for the glutathione synthesis, which impairs antioxidants defenses and increases risk of intoxication of drugs that require glutathione, such as Acetaminophen. This potential increased liver toxicity induced by drugs or other xenobiotics that are detoxified by the glutathione pathway has not been explored in CBS deficiency patients. The experiments should provide answers about the functional role of cysteine and glutathione depletion in CBS deficiency and if N-acetylcysteine might have a place as an adjunct therapy for CBS deficiency.

This is a Phase 1, double-blind (Sponsor-open), placebo-controlled, randomized, dose-escalation, inpatient study using a multiple-ascending dose (MAD) design to assess the safety, tolerability, and PD of SYNB1353 in HVs.

The aim of the research is to investigate the safety and efficacy of EPI-743 treatment in patients with Cbl-C defect and related visual and neurological impairment. Primary Endpoints will be the improvement in visual function as assessed by visual acuity and eye-hand coordination and manual dexterity. Secondary Endpoints will be the improvement in neurologic function, evaluated by a battery of age-appropriated psychophysical tests, and/or in objective electrophysiological tests such as Visual Evoked potentials (VEP) and Electroretinogram (ERG) and/or the change in serum markers of redox state.

Cystathionine beta-synthase deficiency is an inherited disease that results in elevation of a substance called homocysteine (Hcy) in blood and urine. Individuals with this disorder have a very high risk for developing blood clots and are at risk for developing eye and bone abnormalities. Current treatments are generally difficult to follow and can fail. Development of additional therapies has been limited by lack of understanding of how the disease works. The purpose of this study is to see if oxidative stress and inflammation are involved in the disease process and if short-term supplementation with taurine is an effective treatment. Funding source: FDA.