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 physicians guidance at the UPMC Childrens 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 treatments 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 efficacy of Northera Droxidopa in children aged 7 to 17 years with Menkes disease who survived major neurodegenerative effects through early Copper Histidinate treatment. The study focuses on pediatric survivors experiencing dysautonomia symptoms such as dizziness, fainting, low blood pressure, and bowel or bladder issues caused by dopamine-beta-hydroxylase deficiency. This Phase III clinical trial aims to address an important unmet need in this rare disease population. Participants receive oral Northera Droxidopa or placebo capsules indistinguishable from each other in a double-blind, randomized, crossover design. The study uses individualized dose titration of droxidopa, taken twice daily in a freshly prepared liquid suspension. Two four-week treatment periods alternate between active drug and placebo to assess effects on blood neurochemicals, blood pressure, and physical performance. The Orthostatic Hypotension Symptom Assessment OHSA questionnaire is validated during each treatment period. During the trial, participants undergo safety monitoring for serious adverse events over 10 weeks. Researchers measure plasma norepinephrine and dihydroxyphenylglycol levels, systolic blood pressure, daily bowel movements, standing time, and six-minute walk distance at baseline and after each intervention period. The study involves multiple visits to ensure adherence and collect data to determine whether droxidopa improves symptoms of dysautonomia and quality of life in pediatric Menkes disease survivors.

This research aims to collect CD34 hematopoietic stem cells HSC from peripheral blood andor bone marrow, along with mononuclear cells and granulocytes from peripheral blood. 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. The study includes adult patients with primary immune deficiencies or blood disorders and healthy adult volunteers to support the development and scale-up of gene therapies and cell engineering products. The main collection method for HSC is apheresis from peripheral blood after mobilization with daily subcutaneous injections of granulocyte colony stimulating factor G-CSF for 5 to 6 days, sometimes combined with Plerixafor. Some patients may also undergo bone marrow aspiration for clinical or research purposes. Mononuclear cells and granulocytes are collected from peripheral blood by apheresis, with or without pre-treatment using G-CSF alone or combined with dexamethasone, following standard care practices. Collected cells from patients may be used for clinical treatments under separate protocols or for laboratory research, while cells from healthy volunteers are used for research only. Participants provide blood andor bone marrow samples that may be stored or modified for research. Assessments include monitoring cell mobilization and collection through apheresis and bone marrow harvests. The collected cells contribute to laboratory studies of immune deficiencies, stem cell biology, and gene therapy development. The study evaluates the ability to mobilize and collect these cells safely and effectively. Participation involves collection visits and allows for ongoing research and potential clinical use of the samples in 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 THR, 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 T3free 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.

This observational study follows individuals diagnosed with Rett syndrome who have mutations in the MECP2 gene. It gathers detailed information on the signs and symptoms of Rett syndrome as reported by expert clinicians and caregivers. The purpose is to use this data to develop consensus-based care guidelines and support the advancement of clinical trials and drug development for Rett syndrome. Participants are observed over a period of up to five years without receiving any experimental treatments. Data collection focuses on the natural history of the condition, capturing changes and progression as reported by medical experts and caregivers. There is no intervention or drug administration involved in this study. During the study, participants and their caregivers provide information on symptoms and health status. Researchers compile this data to understand the course of Rett syndrome better. The main outcome measured is the natural history over five years. Participants contribute information through routine clinical observations and caregiver reports throughout the study duration.

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.