Mitochondrial Disease

Researchers are exploring and comparing how patients perceive sounds after receiving either cochlear implants or gene therapy for congenital deafness. This study aims to understand differences in speech perception in various environments, music appreciation, and directional hearing between these two treatments. By assessing cognitive and psychological factors alongside auditory development, the study hopes to inform better rehabilitation plans for gene therapy patients. The study includes two groups of congenital deafness patients: those who have cochlear implants and those who have undergone gene therapy for autosomal recessive deafness 9 (DFNB9). Patients receive standard postoperative care and follow-up. The evaluation covers multiple aspects such as speech perception in quiet and noisy settings, cognitive function, psychological status, and auditory cortex growth over time. Participants will be assessed before treatment and at weeks 13, 26, and 52 after intervention. Evaluations include tests of auditory speech perception, cognitive abilities, psychological health, and brain development related to hearing. The study requires participants and their guardians to provide informed consent and cooperate with follow-up visits. Healthy individuals with normal hearing are also included as controls. The goal is to compare outcomes between the two treatments over one year.

Researchers are evaluating the effects of oral TTI-0102 compared to placebo in patients diagnosed with MELAS syndrome, a condition characterized by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. This randomized, double-blind, placebo-controlled study aims to assess the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of TTI-0102 over a treatment period of up to six months in patients aged 16 to 60 years with moderate disease severity. Participants will be randomly assigned to receive either TTI-0102 or a placebo. Treatment begins with a half dose of 2.75 grams once daily for the first week to monitor tolerance, followed by a full dose of 5.5 grams once daily for the remaining weeks. The study includes an initial screening visit, a Day 1 dosing visit, weekly visits during the first week, and alternating clinic visits and phone calls over the first eight weeks. Monthly clinic visits continue from Week 12 through Week 20, with a Study Exit visit at Week 24. Participants may opt to continue in an open-label extension study after completing the initial 24-week period. Throughout the study, participants will undergo various assessments including a 12-minute walk test, safety evaluations, and blood sampling for pharmacokinetic and pharmacodynamic analyses. The primary outcomes measured are changes in functional capacity and the incidence of treatment-emergent adverse events from baseline to Week 24. Secondary outcomes include fatigue levels, quality of life, and pharmacokinetic parameters like peak concentration and exposure. Safety and efficacy will be closely monitored with interim data reviews to guide study continuation.

Maternal and infant health is a key indicator of overall population health, facing new challenges due to rapid socioeconomic changes and environmental issues. This research focuses on understanding the causes of reproductive and pregnancy-related diseases, birth defects, and childhood illnesses by studying families from pregnancy through early life. The goal is to identify genetic, environmental, and behavioral risk factors that affect embryonic development, fetal health, and infant well-being. The project involves recruiting families expecting a child or with newborns and collecting biological samples such as blood, urine, and vaginal secretions at multiple points in time. These samples undergo multi-omics testing, including whole-genome sequencing, metabolite analysis, DNA methylation, protein expression, and microbiome sequencing. Data and clinical information are securely stored and carefully reviewed to ensure ethical, legal, and scientific standards. Participants will sign consent forms, complete questionnaires, and provide biological samples during the study. Researchers will analyze whole-genome sequencing and other molecular data about one year after sample collection to identify biomarkers and develop predictive models for reproductive and developmental diseases. The study includes long-term follow-ups on families to better understand early life risk factors and support prevention strategies for genetic diseases.

Researchers are studying mitochondrial disease, a rare inherited disorder that can cause poor growth, developmental delays, muscle weakness, and other symptoms. This research focuses on understanding how infections affect people with mitochondrial disease and how genes influence their health. The study aims to identify immune responses and other biological markers related to infection and recovery in affected individuals. Participants include people with mitochondrial disease who may or may not be acutely ill and their household or family members. Those with acute infections or those without are grouped separately, along with family members who do not have the disease. The study involves collecting blood samples, reviewing medical records, completing health questionnaires, and may include video exams during illness. Biological samples such as blood and possibly cerebral spinal fluid will be analyzed for immune and genetic markers. Participants will be involved for about one year, with possible extensions if their illness continues. Researchers will perform genetic and immune profiling through blood tests and questionnaires to track health changes and infection responses over time. They will collect data on clinical presentations, healthcare access, and functional status. Personal data will be coded and shared with other researchers while protecting privacy.

Researchers are studying inherited and acquired retinal disorders to better understand changes in photoreceptors, retinal pigment epithelium, and retinal blood vessels. This observational study uses adaptive optics (AO) technology to visualize retinal structures in living patients and compare them to healthy controls. The study aims to evaluate the effects of various treatments and develop AO imaging as a measure of outcomes in retinal diseases. The study plans to enroll about 200 participants including approximately 175 with retinal diseases and 25 healthy controls. Participants will undergo AO retinal imaging using the rtx1 device, which is non-invasive and uses infrared light to capture high-resolution images of the retina. The imaging will be done at baseline, then repeated at 6 months and 1 year to observe any changes or effects of treatment. Participants will provide medical and family history and have their retinal images taken at scheduled visits. The study measures include quantifying cone photoreceptor density and spacing, retinal pigment epithelium density, and retinal blood flow using software within the AO device. Follow-up imaging compares changes over time to assess disease progression or treatment impact. The total participation includes baseline and two follow-up visits over one year.

This research aims to evaluate the potential of transferring mitochondria from a woman's own adipose stem cells to her oocytes during intracytoplasmic sperm injection (ICSI) to improve embryo development and increase the success rate for women who have experienced multiple failed IVF attempts. Embryo quality is crucial for successful assisted reproductive technologies, and factors such as age and genetics can affect this. Since oocytes depend heavily on mitochondria for energy, boosting mitochondrial content may enhance embryo quality in patients with repeated IVF failures. In this study, mature sibling oocytes will be randomly divided into two groups. One group will undergo conventional ICSI, while the other group will receive mitochondria transplanted from adipose-derived stem cells together with ICSI (called Mito-ICSI). Viable blastocysts from both groups will be biopsied for genetic testing to check for chromosome abnormalities. This randomized, double-blind study compares the outcomes of these two approaches. Participants will provide adipose tissue samples through subcutaneous liposuction and consent to have all embryos frozen and biopsied for genetic testing. Researchers will monitor embryo development rates up to 8 weeks after the procedure and track pregnancy outcomes, such as clinical pregnancy rates, live births, and complications, over up to 24 months. The study involves close monitoring and assessments to evaluate the effects of the mitochondrial transfer on embryo quality and pregnancy success.

Researchers are evaluating a new newborn screening method called BeginNGS, which uses whole genome sequencing to screen for hundreds of genetic diseases. This adaptive clinical trial aims to compare BeginNGS with the current standard state newborn screening to assess its usefulness, acceptability, feasibility, and cost effectiveness. The study focuses on newborns less than 28 days old, with the goal of improving early diagnosis and treatment of many genetic diseases not covered by standard screening. Participants will have a blood sample taken to perform the BeginNGS test in addition to the routine state newborn screening. BeginNGS targets over 400 genetic diseases and adapts over time by adding or removing disorders based on emerging evidence of treatment benefits. The study plans to enroll at least 10,000 newborns, with potential expansion up to 100,000, to support broad implementation of this genome sequencing approach. During the trial, newborns and their parents will be involved in providing consent and blood samples. Researchers will compare the clinical utility of BeginNGS to state screening by measuring the proportion of newborns likely to benefit from treatment over five years. The study will also track acceptability, feasibility, cost effectiveness, and accuracy of BeginNGS, with results collected and analyzed over a five-year period.

Researchers are evaluating the effects of conventional exercise and passive exercise through periodic acceleration (pGz) in individuals with primary mitochondrial disease (PMD) and healthy volunteers, as well as exploring these effects in patients admitted to a pediatric intensive care unit (PICU). This multi-aim study compares responses between PMD patients and healthy controls, and also investigates outcomes in critically ill pediatric patients. Participants in Aim 1 will complete three study visits in random order, each involving a different intervention: Cardiopulmonary Exercise Testing (CPET), pGz via a bed device, and pGz via a Gentle Jogger device. Aim 2 participants in the PICU will have two study visits during their admission, involving pedal exercise and pGz using the Gentle Jogger. Interventions include exercise testing, passive exercise with devices, and administration of a contrast agent during vascular ultrasound. During study visits, participants will have blood draws before and after interventions, vascular ultrasounds with contrast, and MRI scans of the lower leg. Various measurements such as oxygen consumption, heart rate, plasma lactate levels, and vasodilation will be assessed. The study also includes surveys and scales to evaluate participant responses. Total participation involves multiple visits with detailed monitoring and assessments under medical supervision.

Researchers are investigating how genetic differences called single nucleotide polymorphisms (SNPs) affect children with type 2 inflammation-related asthma. This observational study compares children diagnosed with asthma who show signs of type 2 inflammation to healthy children. The goal is to better understand how these genetic variations influence asthma development and to support personalized treatment and prevention strategies. The study includes two groups: children with asthma who meet specific inflammation criteria and healthy children. Researchers measure several type 2 inflammation markers, such as the fraction of exhaled nitric oxide, blood eosinophil counts, sputum eosinophil percentages, and serum immunoglobulin E levels. They also assess lung function through tests like forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and peak expiratory flow (PEF). Genetic testing for SNPs is performed to explore differences between groups. Participants will be evaluated during outpatient visits, where lung function tests and inflammation marker measurements will be collected. The main outcomes include type 2 inflammation indicators, pulmonary function measures, and genetic polymorphism data. This process helps researchers identify risk factors and differences in asthma linked to genetics, with the study lasting until December 2025.

This research aims to collect coded biological samples and clinical information from patients with genetic diseases to support future studies. The goal is to identify new gene mutations and explore potential treatment options. The study is observational and involves patients at the Maastricht University Medical Center's Clinical Genetics department. Participants provide biological material that will be stored for genetic research in five key areas: cardiogenetics, intellectual disability and rare diseases, oncogenetics, dermatogenetics, and reproductive genetics. The study utilizes biobanking to preserve samples for future analysis. Genes will be sequenced and compared over an expected average period of six months to discover unknown gene functions. During the study, participants will undergo genetic diagnostics involving the collection of biological samples. Researchers will evaluate genetic data and compare gene sequences as the primary outcome. Participation involves providing consent and samples, with no interventional treatment given. The study will continue through 2035, allowing for long-term research and data collection.