Metachromatic Leukodystrophy

Cognitive problems often occur in people with neurodegenerative diseases. Researchers are exploring how sleep disorders relate to the progression of these diseases by studying their clinical signs, brain imaging, and biological markers. This observational study aims to better understand the mechanisms behind sleep problems in neurodegenerative conditions. Participants will have assessments including neuropsychological tests, brain MRI scans, and electroencephalograms. Biological samples will also be collected to measure markers like plasma Ab2-42 levels. These evaluations will help observe changes in sleep quality, cognitive function, heart rate variability, and other relevant outcomes over time. People in the study will undergo baseline and follow-up tests such as the Pittsburgh Sleep Quality Index (PSQI), Montreal Cognitive Assessment (MoCA), and Addenbrooke's Cognitive Examination (ACE-III). Researchers will monitor sleep patterns and biological markers to track disease progression. The study includes adults aged 30 to 80 years and will continue through June 2030, providing long-term data on sleep disorders linked to neurodegeneration.

Researchers at the University of Texas Health Science Center at San Antonio are studying individuals with chromosome 18 abnormalities to better understand the genetic causes and effects of these conditions. The study aims to identify how growth hormone deficiency and other genetic factors impact brain structure and cognitive function, as well as physical and behavioral traits. The goal is to provide comprehensive medical and educational resources, perform clinical and basic research, and develop treatments to improve the lives of affected individuals. Participants undergo various evaluations including genetic testing of DNA from subjects and their parents to determine genotype. Clinical assessments include testing growth hormone and other hormone levels, psychiatric and neuropsychological evaluations, audiology and ENT exams, brain MRI scans, genetic dysmorphology, neurology, dental, speech pathology, gastrointestinal, orthopedic, and ophthalmologic examinations. These assessments are longitudinal, with participants of a wide age range, and not all tests apply to every participant at every visit. Participants will be involved in thorough clinical evaluations and multiple specialized exams over time to gather detailed health data. These include hormone tests, brain imaging, behavioral and cognitive assessments, and physical exams. Researchers will monitor growth hormone status and other health markers to understand the condition's impact. The study is ongoing and designed to provide long-term data to guide future treatments and support. Total participation time varies depending on individual assessments and follow-up needs.

Researchers are evaluating targeted therapeutic exercises for individuals with neurodegenerative diseases that affect walking. The study aims to improve how clinicians assess disease severity, apply exercise interventions that match the disease pathology, and measure the impact on balance and walking. The research focuses on conditions such as leukodystrophy, ataxia, LBSL, and adrenomyeloneuropathy among others. Participants will engage in an individually designed home exercise program focused on addressing walking impairments. This program will be remotely supervised to test the feasibility of such interventions and to optimize outcome measures that can be used in clinical monitoring and future trials. The exercise intervention will be tailored to each participant's condition and delivered in a home setting. During the study, participants will be assessed on changes in motor function and sleep quality using tools like the NeuroQOL lower extremity measure over a 12-week period. Researchers will monitor balance and walking improvements as well as the feasibility of remote supervision. The study includes healthy volunteers who can stand and walk for specific durations and involves ongoing clinical evaluations to ensure safety and measure progress. Total participation duration and follow-ups are designed to support these goals.

Researchers are studying the progression of rare genetic neurodegenerative disorders that affect the brain. This research aims to better understand how these diseases develop over time and to analyze the effects of different interventions. The study is observational and focuses on disorders such as MLD, Krabbe Disease, ALD, and many other rare conditions affecting the nervous system. Participants are observed without receiving experimental treatments. The study collects data from patients who are receiving standard care, including those who have undergone Hematopoietic Stem Cell Transplantation (HSCT) and those receiving palliative care. Evaluations by a multidisciplinary team occur regularly: every 3 months during the first year, every 6 months in the second year, and once a year thereafter. During these visits, researchers assess key developmental areas including cognitive, language, gross and fine motor skills, and adaptive living skills over a 15-year period. Brain neurodegeneration is monitored using MRI diffusion tensor imaging in patients from birth to 5 years old, while exploratory biomarkers are also collected. This long-term follow-up helps track disease course and intervention outcomes for up to 15 years.

Researchers are studying adults and children affected by several inherited brain diseases including adrenomyeloneuropathy (AMN), cerebral adrenoleukodystrophy (cALD), metachromatic leukodystrophy (MLD), and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). These conditions involve nerve damage and inflammation, and the study aims to understand how immune cells called macrophages contribute to disease progression. This observational study involves 49 participants and explores how genetic mutations affect immune responses linked to these diseases. Participants include affected children and adults as well as healthy controls. The main activity involves collecting one blood sample during a routine medical visit. This sample will be used to analyze macrophage function, including their ability to engulf myelin, their distribution, and certain immune markers. No treatments or interventions are given, as this is a minimal risk study focusing on immune system activity related to these conditions. During the study, researchers will monitor macrophage function and gene activity over a two-year period following blood collection. Participants will have one blood draw during their scheduled medical follow-up. The study also includes healthy children and adults for comparison. The research team will track immune cell profiles and metabolic patterns to better understand how immune responses may influence disease outcomes in these leukodystrophies.

This research investigates Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL), a rare genetic disorder causing progressive problems with movement, coordination, and some cognitive functions. The study aims to understand the range and progression of neuromotor and neurocognitive impairments in individuals with LBSL by reviewing past medical records and performing ongoing virtual assessments. The goal is to better characterize the disease's natural history and link symptoms to genetic factors, helping guide future care and treatment development. Participants will undergo retrospective review of medical charts and imaging studies, along with prospective longitudinal virtual evaluations. These virtual assessments include standardized surveys to measure behavior, social communication, executive function, adaptive skills, and quality of life. Wearable sensor technology and clinical tests like the Timed Up and Go and Long Walk Test will assess ataxia and balance. The study does not involve drug interventions but focuses on detailed observation and data collection. Throughout the study, participants will be involved in virtual assessments and their past medical data will be reviewed to track changes over time. Researchers will measure motor and cognitive function, quality of life, and movement abilities using specialized surveys and wearable devices. The study started in April 2018 and will continue monitoring participants through May 2029, aiming to gather extensive data to inform future supportive therapies and treatment priorities for LBSL patients.

Researchers are studying leukodystrophies, inherited disorders affecting the brain's white matter, which impact about 1 in 7,500 children and have a high mortality rate over 30%. These conditions often cause serious complications like epilepsy, developmental decline, and intellectual disabilities. The study aims to improve diagnosis, care, and understanding of patient outcomes by collecting clinical histories and monitoring disease progression. This observational study is conducted through the Western Leukodystrophy Project at the University of Utah and Primary Children's Hospital, specialized centers for leukodystrophy care. Participants receive diagnosis support, treatment suggestions, and care guideline implementation. The study tracks patient health and disease evolution over time without testing new treatments. Participants are followed for up to 20 years, with yearly check-ins to monitor complications such as spasticity, respiratory and bulbar issues, hypotonia, cerebellar and language problems, and hospitalizations. Brain MRIs are done at enrollment and repeated approximately every five years. Clinical and diagnostic testing occurs at baseline and every three years. The study measures morbidity as the primary outcome, helping researchers understand long-term effects and responses to interventions like bone marrow transplant.

Researchers are conducting a patient registry and natural history study called Coordination of Rare Diseases at Sanford (CoRDS) to support research on rare diseases. CoRDS is an international registry that connects patients with rare, undiagnosed, or uncommon diseases to researchers studying over 7,000 rare diseases. This program aims to help advance treatments and cures by facilitating easy collaboration between patients, advocacy groups, and researchers. It is based at Sanford Research in Sioux Falls, South Dakota, and is free for patients to join and for researchers to access. Participants provide contact, sociodemographic, and health information, which is entered into CoRDS and linked to a unique coded identifier. Examples of collected data include name, mailing address, phone number, email, date and place of birth, sex, gender, ethnicity, family history, and diagnosis-related information. De-identified information may be shared with approved researchers after review by an Institutional Review Board and expert panel. Some data may also be shared with other databases and patient advocacy groups, with protections to prevent misuse for research purposes. Participants are contacted yearly to confirm continued participation and to update their information. If a parent or legal guardian consents for a minor, the participant will be contacted at age 18 to provide their own consent. The primary goal is to accelerate research by connecting individuals interested in rare disease research with scientists over a long period of up to 100 years. There is no treatment given, as this is an observational registry study.

Researchers are collecting and analyzing clinical information and biological samples from people worldwide who have leukodystrophies, a group of genetic white matter brain disorders. The study aims to improve understanding of these diseases, find new genetic causes, develop biomarkers, and track the natural history of leukodystrophies to support future research and treatment development. This project is one of the largest biorepositories for leukodystrophy patients, with nearly 2,000 participants enrolled over more than ten years. Participants include individuals with suspected or confirmed leukodystrophies or related genetic white matter disorders, as well as healthy controls. The study involves collecting clinical data, standardized assessments, and biological samples to achieve multiple goals, such as defining new patient groups, evaluating next-generation genetic testing, understanding disease mechanisms, and following patients' care and outcomes over time. Consent and assent are required for participation, and participants may be contacted for future studies. During the study, researchers gather clinical information, imaging data, and biological samples to track disease progression and care over a period of up to ten years from enrollment. The main outcome is to identify new homogeneous patient groups with unclassified leukodystrophies. Secondary outcomes include evaluating genetic testing methods, understanding disease biology, and maintaining contact with participants for ongoing research. Participation involves providing data and samples and completing assessments to help advance diagnosis and treatment for leukodystrophy patients globally.

Researchers are evaluating the safety and feasibility of giving DUOC-01, a cell therapy derived from umbilical cord blood, as an additional treatment for patients with inherited metabolic diseases (IMD) who show early signs of nerve damage in the central nervous system. These patients are also receiving standard treatment with unrelated umbilical cord blood transplantation (UCBT). The study also aims to describe how effective the combined UCBT and DUOC-01 treatment is in these patients. IMDs are genetic disorders that often cause progressive neurological problems and early death due to enzyme defects and toxic buildup. The study involves administering DUOC-01 intrathecally (directly into the spinal fluid) between 26 and 28 days after the unrelated cord blood transplant. The DUOC-01 cells come from umbilical cord blood and may be from the same donor as the transplant or a second donor. This treatment is given as an adjunct to standard UCBT to help speed up the arrival of donor cells to the central nervous system and prevent disease progression while the transplant takes effect. Participants will be monitored for safety, including checking for toxic reactions 24 hours after the DUOC-01 infusion and neurological effects one month later. Researchers will also assess the treatment's efficacy over 1 to 5 years. Evaluations include neurological exams, brain imaging, and tests of organ function. The study involves patients from 1 week to 21 years old with specific inherited metabolic disorders who have neurologic evidence of disease and are eligible for UCBT. The total duration of participation varies depending on follow-up assessments.