Leukodystrophy

The GENESIS clinical study aims to map HLA genetic variation in the Greek population and evaluate possible correlations with selected underlying diseases. It is a multicenter, prospective, non-interventional clinical study targeting 12,000 subjects over an anticipated duration of 36 months, with the goal of creating a pilot HLA map for medical research and possible clinical applications. Each subject will complete one visit at a participating site and provide demographic information, including date of birth, gender, race, ancestry, height, and weight, as well as information about smoking or vaping, alcohol consumption, arterial blood pressure, diagnosed diseases, and current treatments. Recent clinical laboratory results from up to 12 months before sample collection may also be collected when available, including blood count, metabolic, liver enzyme, and biochemical parameters. Two buccal swabs will be collected from each subject for DNA extraction and HLA genotyping analysis. Selected DNA samples will also undergo low-pass whole genome sequencing to further investigate associations between the HLA region and autoimmune diseases. After the analysis is completed, an individualized ancestry report will be securely available to study subjects if they elect to access it.

Researchers are developing a multicenter registry to collect and share data on pediatric patients who have undergone deep brain stimulation DBS for movement disorders such as dystonia, epilepsy, Tourette syndrome, and mood disorders. The study aims to improve understanding of DBS safety and effectiveness in children, as current data are limited and individual centers often have too few cases for strong research. This registry will support large-scale analyses and help refine DBS as a treatment option for hyperkinetic movement disorders in the pediatric population. The study involves gathering both retrospective and prospective clinical data from multiple pediatric centers. The registry will collect information on surgical techniques, patient outcomes, implant sites, and long-term effects of DBS. This collaborative data-sharing approach enables comprehensive evaluation of which patients benefit most from DBS and how it impacts their quality of life over time. Participants include children aged 0 to 18 years who have already received or are scheduled to receive DBS for neurological movement disorders. Data will be collected over five years to monitor safety, efficacy, and quality of life outcomes. The study does not involve treatment administration but focuses on gathering and analyzing clinical information. Parental or legal guardian consent is required for prospective participation.

This research aims to evaluate postoperative respiratory complications PORC in children with obstructive sleep apnea OSA who undergo adenotonsillectomy. It combines data from two centers University Hospital Antwerp and Heim Pal National Pediatric Institute in Hungary. The study examines how common these complications are and whether they vary according to different health conditions such as obesity, craniofacial malformations, Down syndrome, or neurological disorders that affect airway muscle tone. Data come from a retrospective analysis of electronic health records originally collected in two prospective studies. These records include children who had adenotonsillectomy for OSA, with postoperative care following a set protocol. The study looks at factors like the obstructive apnea-hypopnea index, oxygen levels during sleep studies, age at surgery, and presence of other health conditions to understand their relationship with PORC and to help develop a management plan. Participants information was collected without needing additional consent because it uses existing anonymized data. Researchers assess the prevalence of PORC within 24 hours after surgery and analyze how different factors affect this risk. This study does not involve new treatments but reviews existing data to improve postoperative care. The study includes children aged 1 to 18 years who had adenotonsillectomy for OSA, with follow-up limited to the immediate postoperative period.

Researchers are investigating epilepsy-dyskinesia syndromes, which are rare genetic diseases causing both movement disorders and epilepsy in children. This multinational retrospective survey, supported by the International Parkinson and Movement Disorder Society, aims to collect detailed clinical and molecular data to better understand these conditions. The study focuses on identifying patterns in disease features, progression, and genetic links to improve knowledge and support precision medicine. The study collects previously recorded data from multiple countries, harmonizing information on clinical features, disease progression, age of onset, genetic variants, and coexisting neurological conditions. By standardizing this data, the survey addresses challenges in rare disease research like small, dispersed patient groups and inconsistent protocols. The goal is to build a shared clinical database and analyze how movement and seizure disorders relate at both clinical and molecular levels. Participants are children aged 0 to 18 years with diagnosed movement disorders linked to specific genetic variants. The study reviews existing medical records and genetic information without new treatments or interventions. Researchers will assess the disease spectrum, how movement disorders affect quality of life, and the effectiveness of symptomatic treatments over one year. The study encourages international collaboration to advance understanding and improve care for these rare conditions.

Researchers are studying BBP-812, an investigational gene therapy using an AAV9-based vector, to evaluate its safety, tolerability, and pharmacodynamic effects in children with Canavan disease. Canavan disease is a very rare, severe, and fatal disorder with no approved treatments. BBP-812 is designed to deliver a gene called ASPA to restore its expression in brain and other cells. Participants will receive a single intravenous infusion of BBP-812. The study includes a dose-finding phase where participants receive either a low or high dose of BBP-812 on Day 0, followed by an expansion phase where participants receive the selected dose from the earlier phase. This gene therapy is given only once during the study. During the trial, participants will be closely monitored through clinical evaluations, urine and brain imaging tests measuring N-acetylaspartate levels, and assessments of motor, cognitive, communication, and adaptive functions up to one year after infusion. Safety is tracked by recording any adverse events. The total study duration includes baseline assessments and follow-ups up to 12 months post-treatment.

This research aims to evaluate the long-term safety outcomes of patients with Cerebral Adrenoleukodystrophy CALD who have been treated with elivaldogene autotemcel eli-cel, tradename Skysona in a real-world, post-marketing setting. The study particularly focuses on tracking newly diagnosed malignancies and assessing major functional disability-free survival over time in participants with more advanced early active CALD. This observational study includes a specific subpopulation required by the US FDA as part of accelerated approval conditions. Participants in this registry study will be followed for up to 15 years after receiving eli-cel treatment. No new investigational drug will be given during the study. The study plans to enroll 120 participants treated with eli-cel, including a subgroup of 24 participants with more advanced early active CALD, tracked separately for effectiveness outcomes. Data will be collected longitudinally to assess the safety and effectiveness of eli-cel over this extended period. During the study, participants will receive follow-up care by US-based physicians who can submit required data. Researchers will monitor adverse events including malignancies and insertional oncogenesis, as well as survival without major functional disability. Other evaluations include overall survival, serious adverse events, and detailed genetic analyses in the subpopulation with newly diagnosed hematologic malignancies. This long-term observational approach allows comprehensive safety and outcome data collection over 15 years post-infusion.

Researchers are conducting a prospective, observational registry study on Adrenoleukodystrophy ALD, including patients with confirmed or presumed ALD mutations. The study aims to understand the natural history, disease progression, and outcomes in affected individuals, including children, adolescents, adults, and women with ALD. The research also seeks to develop biomarkers from collected biospecimens to potentially predict disease progression and support future interventions. Participants provide medical histories and allow collection of various biospecimens such as buccal swabs, blood, stool, and urine samples, which are stored in a biorepository. The study collects clinical and epidemiological data through medical record reviews and self-reported questionnaires every six months. Eligible participants include those diagnosed by newborn screening, family history, or other means and those with confirmed or presumed mutations. During the study, participants may be asked to provide longitudinal samples and medical information over a period of up to 10 years. Researchers monitor clinical data to better understand disease progression and gather valuable biological data. The registry and biorepository serve as resources for ongoing and future ALD research, supporting efforts to identify prognostic markers and improve patient care.

Researchers are conducting an observational prospective study to build a large-scale multiomic database of adult patients undergoing advanced imaging studies. The study focuses on using recently introduced photon counting CT scanners and high-field 3T MRI scanners to explore latent imaging information, called opportunist features, which may provide new insights into disease risk and progression. This research aims to improve understanding of pathological mechanisms and enhance diagnostic and prognostic accuracy in fields such as oncology, neurology, pulmonary, and cardiovascular diseases. The study enrolls consecutive adults undergoing advanced imaging examinations at a single center using the Photon Counting CT scanner Neaotom Alpha, Siemens and 3T MRI MR 7700, Philips. Imaging raw data along with conventional images will be stored. Clinical, demographic, and laboratory information, including genetic test results when available, will be collected at enrollment. Blood samples for lab analysis will be taken during contrast media administration when applicable. Annual updates through clinical visits, telehealth, or phone interviews will be conducted to gather follow-up clinical, lab, and imaging data over a 10-year period. Participants will be asked to provide informed consent and undergo routine imaging and clinical assessments as part of their standard care. Data collection includes questionnaires, interviews, and automatic record updates when examinations occur at the study site. Researchers will monitor the development of imaging signatures linked to disease prevention, diagnosis, and treatment. The primary outcome is the creation of a comprehensive multiomics archive to support broad scientific research, with yearly follow-ups for up to 10 years.

Researchers are conducting a prospective, single-arm observational study to collect data from whole-body magnetic resonance imaging WB-MRI scans of up to 100,000 adult participants aged 18 and older across multiple clinical sites in the United States. The study aims to evaluate the accuracy of WB-MRI screening in predicting clinically significant diseases, including cancer, metabolic diseases, aneurysms, and neurologic disorders, in people interested in proactive and advanced preventive healthcare. Participants must meet specific inclusion and exclusion criteria to ensure safety and appropriate enrollment. Participants will undergo a whole-body MRI scan as the primary procedure of the study. The study does not involve any treatment but focuses on diagnostic imaging to detect and assess clinically significant diseases. The study plans to follow participants for up to 10 years to monitor and evaluate outcomes related to clinically significant disease diagnoses and oncological findings using established scoring systems such as the ONCO-RADS score. During the study, participants will provide clinical, demographic, and medical history information and complete consent procedures. Researchers will collect and analyze data from the MRI scans and track diagnoses over the follow-up period. The study includes safety monitoring to exclude individuals with contraindicated medical devices or conditions that could pose risks. Participation involves attendance at clinical sites for imaging and data collection, with long-term follow-up to assess health outcomes over up to a decade.

Researchers are evaluating Fosigotifator, an investigational oral drug, for treating Vanishing White Matter VWM disease in adult, pediatric, and infant participants. This open-label, multiple cohort Phase 1b2 study aims to assess the drugs safety, tolerability, pharmacokinetics, and exploratory efficacy over a 201-week period. Participants are grouped into cohorts based on age, ranging from adults 18 years and older to children as young as 6 months. All participants receive Fosigotifator orally throughout the study. The study includes multiple cohorts adults, adolescents, younger children, and infants. Each cohort undergoes treatment and monitoring according to the protocol. Throughout the study, participants attend regular visits for medical assessments, blood tests, questionnaires, and monitoring for side effects. Researchers evaluate treatment-emergent adverse events, vital signs, ECG changes, clinical lab tests, and changes in mental health using the Columbia-Suicide Severity Rating Scale. Pharmacokinetic measures of Fosigotifator plasma concentration are tracked up to approximately 96 weeks, and MRI changes are assessed up to about 192 weeks. The total study duration extends up to 201 weeks, with ongoing safety and efficacy monitoring.