Menkes Disease

Researchers are exploring the relationship between metal elements and the development of radiation-induced oral mucositis (RIOM) in patients treated for head and neck tumors, such as nasopharyngeal carcinoma. This observational study aims to understand how metal levels may predict the occurrence and severity of RIOM, a common and painful side effect of radiotherapy that significantly affects patients' quality of life and treatment success. The study will follow patients who are undergoing radiotherapy for head and neck tumors. It will observe changes in metal elements over time and analyze how these changes relate to severe RIOM. The research does not involve experimental treatments but focuses on collecting data throughout the radiotherapy process and after, with a monitoring period lasting up to one year. Participants will be regularly assessed for the incidence and duration of severe oral mucositis, quality of life, and other radiation-related side effects. The study will include laboratory tests and clinical evaluations to monitor these outcomes. The total observation period for each participant can last up to one year following radiotherapy, allowing a comprehensive review of RIOM and its possible predictors.

Researchers are collecting clinical data from patients with various non-malignant disorders undergoing hematopoietic stem cell transplantation (HSCT) using a reduced-intensity chemotherapy-based regimen. This regimen includes alemtuzumab and other drugs and aims to reduce graft failure and help immune system recovery. The study follows patients with conditions like primary immunodeficiency, inherited metabolic disorders, hereditary anemias, and inflammatory diseases to better understand treatment outcomes. Participants will receive one of three types of stem cell transplants: umbilical cord blood, bone marrow, or peripheral blood stem cells. All receive a reduced-intensity conditioning regimen that involves alemtuzumab, melphalan, thiotepa, fludarabine, and hydroxyurea, administered according to the treating physician's guidance at the UPMC Children's Hospital of Pittsburgh. This observational study gathers medical data without altering standard care. During the study, researchers will monitor outcomes such as the occurrence of acute graft versus host disease (GVHD) and overall survival for up to five years after transplantation. They will also assess engraftment levels, the timing of immune system recovery, the use of immunosuppressant medications, and donor leukocyte infusions. Medical information will be collected from patients' charts after informed consent, with follow-up extending up to five years to evaluate long-term results.

Researchers are evaluating the efficacy, safety, and tolerability of zeleciment rostudirsen (DYNE-251), given intravenously every 4 weeks, in ambulatory male children and adolescents aged 4 to 18 years with Duchenne muscular dystrophy (DMD) who have a specific mutation suitable for exon 51 skipping. This Phase 3 study aims to provide important information about this treatment option for this group of patients with DMD. The study includes three distinct periods: a Screening period lasting up to 6 weeks, a Placebo-Controlled Period of 72 weeks where participants are randomly assigned to receive either zeleciment rostudirsen or placebo every 4 weeks, and an open-label Long-Term Extension Period of up to 96 weeks during which all participants receive the study drug every 4 weeks. This design allows researchers to compare the treatment to placebo and then assess longer-term effects. Participants will be closely monitored throughout the study with regular assessments including the primary outcome of Rise From Floor (RFF) velocity measured at baseline and Week 73. Various secondary measures such as walking speed, stair climbing ability, lung function, patient global impressions, blood creatine kinase levels, and safety through adverse event monitoring and blood drug levels will be collected up to Week 169 or study completion. The total study duration including the extension is up to approximately 168 weeks. This thorough evaluation helps understand the treatment’s impact and safety over time.

Researchers are studying adults with rare and complex genetic syndromes that affect multiple body systems and often include intellectual disability. These patients typically receive specialized care from multiple specialists during childhood, but as medical advances have extended life expectancy, many are now living into adulthood. The study aims to understand the medical needs, comorbidities, medication use, and quality of life impacts for adults with these rare syndromes, addressing a gap in adult care and guidelines. This research involves a retrospective review of medical files, including medical history, laboratory results, additional tests, and records of physical and psychological complaints. There is no active treatment or intervention, as the study collects and analyzes existing data to gain insights about health issues and medication adaptations needed for these syndromes. Participants' medical records will be analyzed to evaluate the presence of physical health problems, laboratory values, physical and psychological complaints, and medication use over a one-year period. The study uses statistical software for analysis and aims to improve understanding of adult care needs for these rare genetic conditions. The study began in October 2018 and will continue through January 2030.

Researchers are evaluating the safety, tolerability, dosing, and effectiveness of Northera (Droxidopa) in children aged 7 to 17 years who survived the major neurodegenerative effects of Menkes disease after early treatment with Copper Histidinate. This clinical trial focuses on pediatric survivors who experience symptoms of dysautonomia, such as dizziness, orthostatic hypotension, and bowel or bladder dysfunction, caused by a deficiency of the enzyme dopamine-beta-hydroxylase. The study aims to improve blood neurochemical levels, increase systolic blood pressure, and enhance quality of life. Participants will receive oral doses of Droxidopa or matching placebo capsules in a double-blind, randomized crossover design. Doses will be carefully adjusted for each child, with the medication given twice daily in a liquid suspension form prepared from capsules and simple syrup. Each treatment period lasts four weeks, with two treatment phases assessing active drug and placebo effects. The study will also validate a questionnaire assessing orthostatic hypotension symptoms for this population. During the trial, children will be closely monitored for safety and treatment effects through blood tests measuring neurochemical levels, blood pressure readings, and physical tests such as standing time and six-minute walk distance. Researchers will track any adverse events over ten weeks and evaluate symptoms through questionnaires. Participants will attend multiple study visits and are expected to follow the prescribed medication schedule while undergoing assessments of their physical and neurological function.

This research aims to collect CD34+ hematopoietic stem cells (HSC), mononuclear cells, and granulocytes from peripheral blood and bone marrow of adults. These cells will be used in laboratory studies and clinical treatments to develop new cell therapies for patients with inherited or acquired immune or blood disorders. Both healthy adult volunteers and adult patients with primary immune deficiencies or blood disorders may participate to support research and clinical therapy development. Most participants will undergo daily injections of granulocyte colony stimulating factor (G-CSF) for 5 to 6 days to help move HSC into the blood, followed by apheresis collection. Some patients may have bone marrow collected through aspiration or harvesting for clinical or research use. Mononuclear cells and granulocytes may be collected from blood with or without pre-treatment using G-CSF and dexamethasone. Collected cells are used for gene therapy development, cell engineering, and laboratory studies to understand disease mechanisms and improve treatments. Participants will be involved in cell collection procedures such as apheresis or bone marrow aspiration. Researchers will monitor cell mobilization and collection success, perform laboratory studies on the collected cells, and store samples for future research or clinical use. The study tracks outcomes including cell mobilization, collection, and laboratory research results. Participants may contribute to ongoing development of gene therapies or cellular treatments under separate approved protocols.

Researchers are evaluating a reduced-intensity conditioning (RIC) regimen for patients with non-malignant disorders who need a hematopoietic stem cell transplant (HSCT). This study focuses on diseases such as thalassemia, sickle cell disease, primary immunodeficiencies, metabolic disorders, and other inherited conditions. The goal is to assess if RIC before transplant can improve outcomes by reducing complications and transplant-related mortality compared to the standard myeloablative conditioning. The treatments being studied include a conditioning regimen with Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa given before stem cell transplants from umbilical cord blood, bone marrow, or peripheral blood stem cells. Two groups are involved: one receiving double cord blood transplants for transfusion-dependent anemia or higher rejection risk, and another receiving bone marrow or peripheral blood transplants. The study uses lower chemotherapy doses to prepare patients, aiming to help donor stem cells engraft successfully while decreasing side effects on organs. Participants will be monitored for transplant success and side effects over time, including immune recovery, rates of infections, graft-versus-host disease, organ toxicity, and neurodevelopmental progress for up to one year after transplant. Researchers will also track donor cell engraftment and blood counts. The total participation may last several months to years, with follow-up visits to evaluate long-term outcomes and transplant effectiveness.

Researchers are investigating thyroid hormone resistance caused by mutations in the thyroid hormone transporter (MCT8) or the thyroid hormone receptor alpha (THRα), conditions that affect brain development and function. These mutations can lead to severe intellectual disabilities, developmental delays, and movement disorders despite normal thyroid hormone production. The study aims to improve diagnosis by using the serum free T3/free T4 ratio as a screening tool and to explore genetic regulation and mutations contributing to thyroid hormone resistance. This observational registry study, called "DEEPTYPE," collects detailed retrospective and prospective clinical data from patients with coding or non-coding mutations in the SLC16A2 or THRA genes. The registry identifies patients with milder symptoms or non-coding mutations and groups patients based on their genetic profiles. There is no intervention or treatment involved; the study focuses on documenting and understanding the full spectrum of these conditions. Participants will have their neurological development, motor skills, and body measurements tracked over a period of five years. Researchers will assess various clinical and biochemical markers, including thyroid hormone levels, response to therapies, cerebrospinal fluid components, and movement disorder evaluations. This comprehensive monitoring aims to characterize the clinical features and progression of thyroid hormone resistance, supporting future clinical trial readiness and improved patient care.

Researchers are conducting a long-term observational study called the Rett Syndrome Registry to gather detailed information about individuals diagnosed with Rett syndrome who have MECP2 mutations. This study aims to collect data from Rett syndrome experts and caregivers about the signs and symptoms experienced by those with this condition. The goal is to help develop standardized care guidelines and support the creation of better clinical trials and drug development focused on Rett syndrome. This study does not involve treatments or drugs but focuses on observing and recording real-world data over time. Participants include males and females with a loss of function mutation in the MECP2 gene. The study collects information continuously to understand the natural history of Rett syndrome over a 5-year period. Participants and their caregivers will provide data about symptoms and experiences related to Rett syndrome. This may involve regular assessments and reporting to help researchers monitor changes and progression. The study measures the natural history of the condition and aims to improve future care and research. Participation may last up to five years, with ongoing data collection and observation.

Researchers are investigating differences in serum biomarkers among women with different ovarian functions, including those with diminished ovarian reserve, premature ovarian insufficiency, and normal ovarian function. This observational study aims to understand how these biomarkers correlate with ovarian health by comparing affected women to those with normal menstruation and hormone levels. The study involves collecting blood samples from women in three groups: those with diminished ovarian reserve, those with premature ovarian insufficiency, and healthy controls with regular menstruation. The blood tests will measure levels of copper ions, iron ions, ceruloplasmin, CuZn superoxide dismutase, and malondialdehyde, among other related biomarkers associated with copper and iron metabolism and oxidative stress. Participants will provide blood samples during the 2nd to 4th day of their menstrual cycle or during the enrolled week for amenorrhea patients. Researchers will analyze these samples to assess the biomarkers and evaluate ovarian function. The study involves informed consent and includes women aged 18 to 45, with some groups having specific hormone level criteria. The trial will continue until November 2025, with data collected to better understand ovarian aging and function.