Metachromatic Leukodystrophy

Cognitive problems are common in neurodegenerative diseases, and this study aims to better understand how sleep disorders relate to the progression of these diseases. Researchers will explore clinical signs, brain imaging, and biological markers associated with sleep problems in people with neurodegenerative conditions. Participants will undergo various assessments including neuropsychological testing, brain MRI scans, electroencephalograms, and biomarker data collection. These evaluations will help track changes related to sleep disorders alongside neurodegenerative disease features. During the study, participants' sleep quality will be measured using tools like the Pittsburgh Sleep Quality Index (PSQI). Data on sleep patterns, daytime sleepiness, and other related symptoms will be gathered to understand the relationship between sleep disturbances and neurodegenerative disease progression.

Researchers at the University of Texas Health Science Center at San Antonio are investigating individuals with chromosome 18 abnormalities, including those with growth hormone deficiency and brain microstructural changes. The study aims to understand how the genes affected by chromosome 18 deletions contribute to physical and behavioral differences and to develop appropriate therapies. This research serves as an international medical and educational resource for families and promotes both clinical and basic research related to chromosome 18 disorders. Participants undergo a variety of evaluations, including growth hormone stimulation tests, measurements of thyroid and sex hormones, and psychiatric and neuropsychological assessments. Additional examinations include audiological, ENT, brain MRI, genetic dysmorphology, neurology, dental, speech pathology, gastrointestinal, orthopedic, and ophthalmologic evaluations. These assessments help gather comprehensive data to correlate genetic findings with clinical features. The study involves longitudinal phenotypical assessments across a wide age range, with some participants evaluated multiple times. Procedures include blood tests, imaging, physical exams, and standardized testing tailored to age and ability. Researchers monitor growth hormone levels and other hormones, brain structure, behavior, and physical health. The goal is to track these outcomes over time to better understand the condition and inform treatment approaches.

Researchers are studying how targeted exercise programs can help people with neurodegenerative diseases that affect walking. The purpose is to better assess disease severity, apply the right type of exercise, and measure how well these exercises improve balance and walking. The study also aims to test if exercise programs can be effectively supervised remotely and how to best monitor progress from afar. Participants will engage in a home exercise program designed to address walking limitations caused by their condition. This behavioral intervention will be remotely supervised to ensure safety and proper technique. The study will explore the feasibility of this approach and optimize ways to measure outcomes remotely, supporting future clinical trials. During the study, participants will undergo assessments to track changes in balance and walking ability. Researchers will use specific outcome measures, including changes in lower extremity function over 12 weeks. The study will monitor participants' progress and safety remotely, with the total involvement lasting at least 12 weeks.

Researchers are studying the progression of rare genetic neurodegenerative disorders that affect the brain. This study aims to better understand how these diseases develop over time and how different interventions may impact their course. The conditions studied include a variety of specific disorders such as MLD, Krabbe Disease, ALD, MPS types, Batten Disease, and several others related to lysosomal storage and leukodystrophies. Participants will be observed through two main approaches: collecting information on the natural progression of these diseases (palliative care) and following patients who have received hematopoietic stem cell transplantation as part of their clinical care. Evaluations will be conducted by a multidisciplinary team at scheduled intervals—every 3 months during the first year, every 6 months in the second year, and annually thereafter. During the study, participants will undergo assessments of cognitive, language, gross motor, fine motor, and adaptive living skills development over a 15-year period. These evaluations will help track disease progression and the long-term effects of treatments. The study focuses on gathering detailed data to improve understanding of these rare conditions and support future care strategies.

This research investigates the role of innate immunity in influencing disease progression in several inherited leukodystrophies, including X-linked Adrenoleukodystrophy (X-ALD), Metachromatic Leukodystrophy (MLD), and Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP). These diseases affect both children and adults and display variable symptoms and progression. The study focuses on how genetic mutations in these conditions might cause specific immune responses contributing to disease development, especially involving microglia and macrophages, the immune cells in the central nervous system. Participants will provide one blood sample during a routine medical follow-up visit. This open-label study includes 49 subjects with diagnoses of childhood or adult forms of these leukodystrophies or individuals without neurological disease serving as controls. The study examines macrophage activation patterns by analyzing blood samples for monocyte distribution, myelin phagocytosis capacity, and HLA levels, all related to immune cell function. Participants will be involved in a single blood draw, and their clinical history and neurological status will be noted. Researchers will measure macrophage functionality two years after blood collection to assess immune system changes related to these diseases. The study includes children and adults, with follow-up limited to the initial sample collection and later laboratory analysis, ensuring minimal risk. Safety and consent procedures are followed for both pediatric and adult participants.

This research focuses on Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL), a rare genetic disorder causing progressive cerebellar ataxia, spasticity, and sensory issues. The study aims to better understand the natural history of LBSL by examining the range of neuromotor and neurocognitive impairments and their relationship to quality of life. It seeks to clarify genotype-phenotype correlations and identify key symptoms that could guide supportive care and future treatments. The study involves retrospective chart and imaging reviews alongside prospective longitudinal virtual assessments of individuals diagnosed with LBSL. No specific treatments or interventions are provided as part of this study. Instead, researchers will gather detailed clinical, neurocognitive, and neuromotor data through standardized surveys and wearable sensor technology to assess balance, ataxia, and functional abilities. Participants will be involved through virtual assessments and medical record reviews over the study period. Researchers will use neurocognitive surveys to evaluate behavior, social communication, executive function, adaptive function, and quality of life. Physical function will be measured using wearable sensors and clinical tests such as the Timed Up and Go Test and Long Walk Test. Data collected will help track disease progression and improve understanding of the impact of LBSL on daily life and functioning.

Inherited leukodystrophies are rare genetic disorders affecting the white matter of the brain, occurring in about 1 in 7,500 children. These conditions have a high mortality rate exceeding 30% and can cause serious complications such as epilepsy, developmental regression, and intellectual disabilities. Diagnosing leukodystrophies is challenging and requires specialist evaluation. The study aims to better diagnose, manage, and understand the clinical progression and outcomes of people with these disorders. The study is conducted by the Western Leukodystrophy Project at the University of Utah and Primary Children's Hospital, a certified Leukodystrophy Care Network Center. It supports diagnosis, suggests treatment options, and helps implement care guidelines. The research focuses on following patients over time to gather detailed clinical histories and assess outcomes to improve care for individuals with leukodystrophies. Participants will be followed for up to 20 years, with check-ups approximately once per year. Evaluations include physical and neurological exams to monitor health status and disease progression. The main outcome measured is morbidity throughout the study duration, helping researchers understand the long-term impact of leukodystrophies and effectiveness of care strategies.

Researchers are developing the Coordination of Rare Diseases at Sanford (CoRDS), a centralized international registry based at Sanford Research in Sioux Falls, South Dakota. This program serves patients diagnosed with rare disorders, diseases of unknown prevalence, or undiagnosed conditions, aiming to connect them with researchers to advance understanding and treatments for over 7,000 rare diseases. The registry is free for patients to join and for researchers to access, facilitating collaboration with patient advocacy groups and various research organizations worldwide. Participants provide contact details, sociodemographic data, and health information including family history and diagnosis-related information through a questionnaire. This data is assigned a unique coded identifier and de-identified information is shared with approved researchers and certain other databases to enhance rare disease research and avoid duplication. Participants may also choose to share their information with patient advocacy groups, which agree not to use the data for research purposes. Consent from a parent or legal representative is obtained for minors, who are contacted at adulthood for consent renewal. During the study, participants are contacted annually to confirm ongoing interest and update their information. Researchers use the collected data to accelerate rare disease research by connecting interested individuals with studies, tracking natural history, and supporting research efforts. The program monitors participation and consent status over time, with the goal of improving understanding and treatment options for rare disorders over a 100-year period.

Researchers are studying leukodystrophies and other genetic white matter disorders that affect the brain. These conditions have been difficult to diagnose, with many patients remaining undiagnosed for years despite extensive testing. The study aims to define new groups of patients with unclassified leukodystrophies, improve diagnosis using advanced genetic sequencing, understand disease mechanisms, and track the natural history and care of these disorders to help future research and treatment development. The project collects clinical data and biological samples from patients worldwide as part of the Myelin Disorders Biorepository Project, one of the largest collections of its kind. Participants include individuals with suspected or confirmed leukodystrophy or related brain white matter disorders, as well as healthy controls. The study involves ongoing data and sample collection to support multiple research goals, including discovery of new genetic causes and biomarkers. Participants provide clinical information, undergo standardized assessments, and may provide biological samples for research. Consent and assent are required. The study monitors participants over time to define disease progression and outcomes. The primary outcome is to identify novel homogeneous patient groups over a 10-year period. The long-term goal is to improve diagnosis, care, and future clinical trials for these rare disorders.

Researchers are evaluating the safety and feasibility of using DUOC-01, a therapy made from umbilical cord blood-derived cells, as an additional treatment for patients with inherited metabolic diseases that cause early damage to the brain's protective myelin. These patients are undergoing standard treatment with unrelated umbilical cord blood transplantation (UCBT). The study also aims to describe how effective this combined treatment is in slowing or stopping disease progression in these children and young adults. The study involves intrathecal administration of DUOC-01, meaning the cells are given directly into the fluid around the spinal cord, alongside the standard UCB transplant. DUOC-01 cells may come from the same or a different umbilical cord blood donor than the transplant. This approach is intended to speed up the arrival of donor cells to the brain and help prevent further neurological damage while the transplant takes effect. Participants will be closely monitored for safety, including checking for any infusion-related toxicity within 24 hours and neurological side effects one month after treatment. Evaluations include clinical exams, neuroimaging, and various neurological tests to assess disease status. The study includes patients aged from 1 week to 21 years with specific inherited metabolic disorders and neurological signs, with planned follow-up to understand both safety and treatment effects over time.