Active clinical trials for "Genetic Diseases, X-Linked"

Background: Smith-Lemli-Opitz Syndrome (SLOS) is a genetic disorder. It can cause birth defects and developmental delays. There is no cure for SLOS or other inherited diseases related to cholesterol production or storage. The data gained in this study may help researchers find ways to measure how well future treatments work. Objective: To learn more about SLOS and related disorders and how these diseases affect participants and relatives. Eligibility: People of any age who have or are suspected to have SLOS or another inherited disease related to cholesterol production or storage. Relatives are also needed. Design: Participants will be screened with a medical record review. Participants will have visits every 6 to 12 months. They will have a physical exam. They will fill out a survey about their medical and behavioral history. They may have an eye exam. They may have a neurodevelopmental assessment. They may have a hearing test. Their outer and middle ears may be examined. Their ability to speak, understand speech, eat, and swallow may be assessed. They may get X-rays while they chew and swallow. Their functional ability and needs for adaptive devices or braces may be assessed. They may have a lumbar puncture. Photographs may be taken of their face and body. Participants who cannot visit the NIH and relatives will have a virtual visit once a year. They will talk about their medical history and symptoms. They give blood, urine, and skin samples at a lab near their home. They will fill out a survey about their medical and behavioral history. Participation will last for several years.

This study will investigate reproductive genetic carrier screening (RGCS) in 10,000 couples across Australia. Carrier screening for approximately 1300 genes associated with severe, childhood-onset, X-linked and autosomal recessive conditions will be performed on each member of the couple. A combined result will be issued indicating whether the couple has a 'low' or 'increased' risk of having a child with a genetic condition. It is anticipated that 1-2% of couples will be at an increased risk of having an affected child. The study will evaluate all aspects of the RGCS program to assess the feasibility and acceptability of a publicly-funded population-wide RGCS program, including: education of recruiting healthcare providers education of participating couples implementation and uptake of RGCS frequency of increased-risk couples and their reproductive decisions psychosocial impacts ethical issues health economic implications health implementation research

The Rett Syndrome Registry is a longitudinal observational study of individuals with MECP2 mutations and a diagnosis of Rett syndrome. Designed together with the IRSF Rett Syndrome Center of Excellence Network medical directors, this study collects data on the signs and symptoms of Rett syndrome as reported by the Rett syndrome experts and by the caregivers of individuals with Rett syndrome. This study will be used to develop consensus based guidelines for the care of your loved ones with Rett syndrome and to facilitate the development of better clinical trials and other aspects of the drug development path for Rett syndrome.

The research goal of this study is to obtain CD34+ hematopoietic stem cells (HSC) from peripheral blood and/or bone marrow, and Mononuclear Cells (lymphocytes and monocytes), and granulocytes (grans) from peripheral blood that will be used in the laboratory and/or in the clinic to develop new cell therapies for patients with inherited or acquired disorders of immunity or blood cells. Development of novel cellular therapies requires access to HSC, Mononuclear Cells and/or granulocytes as the essential starting materials for the pre-clinical laboratory development of gene therapies and other engineered cell products. HSC or blood cells from healthy adult volunteers serve both as necessary experimental controls and also as surrogates for patient cells for clinical scale-up development. HSC or blood cells from patients serve both as the necessary experimental substrate for novel gene therapy and cellular engineering development for specific disorders and as pre-clinical scale up of cellular therapies. Collection of cells from adult patients collected in the NIH Department of Transfusion Medicine (DTM) under conditions conforming to accepted blood banking clinical practice may also be used directly in or cryopreserved for future use in other NIH protocols that have all required regulatory approvals allowing such use. In summary, the research goal of this protocol is the collection of HSC or blood cells that may be used for both laboratory research and/or for clinical treatment in other approved protocols.

The primary objective of this study is to obtain long term safety data of ataluren in male participants with nonsense mutation dystrophinopathy (who participated and completed a previous Phase 3 study of ataluren [PTC124-GD-020-DMD {NCT01826487}]) to augment the overall safety database. Screening and baseline procedures are structured to avoid a gap in treatment between the double-blind study (PTC124-GD-020-DMD) and this extension study. This study may be further extended by amendment until either ataluren becomes commercially available or the clinical development of ataluren in duchenne muscular dystrophy (DMD) is discontinued.

The purpose of this study is to learn about Smith-Lemli-Opitz Syndrome (SLOS). SLOS is an inherited condition that is caused by the body not making an enzyme as it should. The body needs the enzyme to help make cholesterol. SLOS can cause many health problems including slow growth and development, eating disorders, sleep disorders, behavior disorders, and eye diseases. Severe SLOS leads to birth defects and mental retardation and in many cases early death. The investigators plan to measure cholesterol and other sterol levels, perform clinical observations, whole body testing and imaging (brain MRIs), to learn more about the disease and its progression, differences in the clinical features among individuals with SLOS, and look at the effect of cholesterol supplementation in this condition. The study is an interventional study to characterize disease progression and correlations between clinical, biochemical and physiological features of the disease. The main hypothesis is that dietary cholesterol supplementation does not improve features of SLOS related to the brain (e.g. IQ, behavior).

Objectives: Bipolar disorder (BD) is a chronic and recurrent mental illness characterized by depressive episodes and manic or hypomanic episodes, leading to severe functional impairment and cognitive damage. Unfortunately, it is difficult to accurately distinguish between major depressive disorder (MDD) and BD in the early stages, resulting in misdiagnosis and mistreatment. According to statistics, only 20% of BD patients with initial depressive symptoms receive a correct diagnosis within the first year of onset, with an average delay of 5-10 years from onset to final diagnosis. BD patients are often treated with antidepressant medication systematically due to being diagnosed with MDD, affecting the disease course and clinical outcomes. The current study aims to explore the role of peripheral exosomes as biomarker to distinguish BD from MDD in early stage. Methods: The study includes two stages: the first stage is a case-control study, comparing the concentrations of peripheral blood exosome metabolites (microRNA and related proteins) among three groups (BD patients, MDD patients, and healthy controls, n=30 per group) to identify target microRNA and proteins with statistically significant differences. The "latent class analysis (LCA)" on target microRNA and protein will be performed on all samples to observe whether it can effectively distinguish bipolar disorder, depressive episode, and healthy participants. Then, based on the LCA analysis results, "receiver operating characteristic (ROC)" analysis will be conducted to further determine the optimal concentration cut-off value for each indicator and ultimately determine the target biomarkers. The second stage is a clinical validation study in which subjects, who come from an on-going trial and initiated with a depressive episode and were followed up for five years at least, are divided into two groups (MDD group and BD group, n=20 respectively) based on whether they have hypomanic/manic episodes currently or previously, according to the DSM-5 diagnosed with SCID-5. All target biomarkers will be test in peripheral blood samples reserved at the initial stage to detect whether the diagnosis indicated by the biomarkers is consistent with diagnosis by DSM-5. As well as the accuracy of predicting diagnosis, the correlation between specific biomarkers and treatment response, clinical outcome, and adverse reactions will also be observed. Discussion: It is difficult to explore central nervous system diseases through the peripheral system in the context of the blood-brain barrier. However, exosomes can freely pass through the blood-brain barrier and serve as a good medium for connecting the peripheral system and the central nervous system. This study aims to explore plasma exosome microRNAs and related proteins as biological markers for early diagnosis of bipolar disorder, for example, which microRNAs or proteins are presented in the BD patient group, or what concentrations of microRNAs or proteins are significantly different between the BD patients and MDD patients. Improving the early diagnosis of BD would help develop appropriate clinical intervention strategy, improve the quality of disease management, and significantly reduce the burden of disease. At the same time, this study is also hope to provide a theoretical basis for exploring the pathogenesis of bipolar disorder.

This study is a long-term study of ataluren in participants with nonsense mutation Duchenne muscular dystrophy.

Dystrophinopathy is a disease continuum that includes Duchenne muscular dystrophy, which develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of dystrophinopathy in approximately 10-15 percent (%) of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. The main goal of this Phase 3 study is to evaluate the effect of ataluren on walking ability. The effect of ataluren on physical function, quality of life, and activities of daily living will be evaluated. This study will also provide additional information on the long-term safety of ataluren.

HOPE-2 is a double-blind clinical trial evaluating the safety and efficacy of a cell therapy called CAP-1002 in study participants with Duchenne muscular dystrophy (DMD). Non-ambulatory and ambulatory boys and young men who meet eligibility criteria will be randomly assigned to receive either CAP-1002 or placebo every 3 months for a total of 4 doses during a 12-month period.