An observational study in Leukodystrophy, White Matter Disease and Leukoencephalopathies, sponsored by Children's Hospital of Philadelphia. Recruiting at 23 sites in United States. Per ClinicalTrials.gov, last updated 2025-10-23.
Sponsored by Children's Hospital of Philadelphia · Observational
The Myelin Disorders Biorepository Project (MDBP) seeks to collect and analyze clinical data and biological samples from leukodystrophy patients worldwide to support ongoing and future research projects. The MDBP is one of the world's largest leukodystrophy biorepositories, having enrolled nearly 2,000 affected individuals since it was launched over a decade ago.
Researchers working in the biorepository hope to use these materials to uncover new genetic etiologies for various leukodystrophies, develop biomarkers for use in future clinical trials, and better understand the natural history of these disorders. The knowledge gained from these efforts may help improve the diagnostic tools and treatment options available to patients in the future.
Genetic white matter disorders (leukodystrophies) are estimated to have an incidence of approximately 1:7000 live births. In the past, patients with white matter disease of unknown cause evaluated by the investigator achieved a diagnosis in fewer than 46% of cases after extensive conventional clinical testing. Even when a diagnosis is achieved, the diagnosis takes an average of eight years and this "odyssey" results in testing charges to patients and insurers in excess of $8,000 on average per patient, including patients who never achieve a diagnosis at all. With next generation approaches such as whole exome sequencing, the diagnostic efficacy is closer to 70%, but approximately a third of individuals do not achieve a specific etiologic diagnosis. These diagnostic challenges represent an urgent and unresolved gap in knowledge and disease characterization, as obtaining a definitive diagnosis is of paramount importance for leukodystrophy patients.
Moreover, the mechanisms of disease in many leukodystrophies of known cause are very poorly understood, with little known about the best symptomatic management and, thus, limited standards of care are available for the management of these patients.
The purpose of this study is to: (Aim 1) Define novel homogeneous groups of patients with unclassified leukodystrophy and work toward finding the cause of these disorders; (Aim 2) assess the validity and utility of next-generation sequencing in the diagnosis of leukodystrophies; (Aim 3) establish disease mechanisms in selected known leukodystrophies; (Aim 4) track current care and natural history of these patients to define the longitudinal course and determinants of outcomes in these disorders; (Aim 5) contact subjects for future research studies and/or clinical programs.
This biorepository will use available basic science and clinical research approaches to establish novel diagnoses, biomarkers, and outcome measures for future clinical diagnostic and therapeutic approaches.
Affected subjects will have either a confirmed or suspected diagnosis of leukodystrophy, or a related heritable disorder affecting the white matter of the brain. Healthy controls must be individuals in whom no leukodystrophy or related disorder has been suspected or confirmed.
Inclusion Criteria (Affected Subjects):
Exclusion Criteria (Affected Subjects)
Inclusion Criteria (Healthy Controls)
Exclusion Criteria (Healthy Controls)
- Inability to provide consent.
Define Novel Homogeneous Groups of Patients with Unclassified Leukodystrophy
In patients with an unclassified leukodystrophy, the study team will collect as much information as available from existing medical records including existing clinical evaluations, neuropsychological/rehabilitation evaluations, and results from blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. This data will be evaluated to create nosologic groups amongst patients with unclassified leukodystrophy. Additionally, this aim includes the collection and long-term banking of biological samples in subjects with classified and unclassified leukodystrophies to develop a biorepository. These samples will be compared to samples collected from control subjects, either collected directly from enrolled subjects or through existing banked biological samples.
Time frame: 10 years from enrollment
Assess Validity of Next-Generation Sequencing in the Diagnosis of Leukodystrophies
Unclassified leukodystrophy patients enrolled in this study may undergo next generation sequencing approaches, including research whole exome sequencing (WES), whole genome sequencing (WGS), RNA sequencing and high throughput genomics analysis in parallel to standard clinical testing to achieve novel molecular classifications.
Time frame: 10 years from enrollment
Assess Utility of Next-Generation Sequencing in the Diagnosis of Leukodystrophies
Clinical utility defined as changes in care and clinical state, included changes in medical morbidities, surgeries, pharmacologic management of complications and implementation of disease specific therapies.
Time frame: 10 years from enrollment
Track Current Care of Leukodystrophy Patients
Includes a longitudinal collection of clinical data on diagnostic and therapeutic interventions in leukodystrophy patients and related controls.
Time frame: 10 years from enrollment
Track Natural History of Leukodystrophy Patients
Includes longitudinal collection of clinical data on disease presentation, progression and morbidities.
Time frame: 10 years from enrollment
Establish Disease Mechanisms in Leukodystrophies
Specific leukodystrophies will be selected for further mechanistic study, using clinical and laboratory tools to establish increased understanding of the underlying pathophysiology. The over-riding hypothesis of this aim is that integrated biochemical, genomic, metabolic, histologic and immunologic profiles of patients with leukodystrophy will define downstream pathway changes consistent with primary defects causing white matter disease. Appropriate controls will be used for comparison to disease related samples.
Time frame: 10 years from enrollment
Contact for Future Research Studies and/or Clinical Programs
Individuals enrolled in the study may be informed of other research studies, either at the Children's Hospital of Philadelphia or another site affiliated or not affiliated with this study, that may be of interest to them and/or their their families based on a specific diagnosis or lack thereof.
Time frame: 10 years from enrollment
Plan to share: Yes — IPD will be made available to researchers, sponsors, and other stakeholders. Data Use Agreement (DUA) must be put in place with any recipient of IPD. Only aggregate data will be shared publicly.
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