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NCT Number: NCT03047369

The Myelin Disorders Biorepository Project

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.

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Key information

Conditions

Leukodystrophy 4H Syndrome ADLD AGS ALD ALD (Adrenoleukodystrophy) ALD Gene Mutation ALSP AMN Abnormalities, Multiple Adrenal Gland Diseases Adrenal Insufficiency Adrenoleukodystrophy Adrenomyeloneuropathy Aicardi Goutieres Syndrome Aicardi-Goutieres syndrome Alexander Disease Alexanders Leukodystrophy Allan-Herndon-Dudley Syndrome Arthritis Arthritis, Rheumatoid Attention Deficit Disorder with Hyperactivity Attention Deficit and Disruptive Behavior Disorders Autoimmune Diseases AxD BPAN Bone Diseases Bone Diseases, Developmental Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Brain Infarction Brain Ischemia CADASIL CMT CSF1R Gene Mutation CTX Canavan Disease Carbohydrate Metabolism, Inborn Errors Cardiovascular Diseases Central Nervous System Diseases Cerebral Arterial Diseases Cerebral Infarction Cerebral Small Vessel Diseases Cerebrotendinous Xanthomatoses Cerebrovascular Disorders Charcot-Marie-Tooth Charcot-Marie-Tooth Disease Cockayne Syndrome Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Connective Tissue Diseases DNA Repair-Deficiency Disorders Dementia Dementia, Vascular Demyelinating Diseases Digestive System Diseases Dry Eye Syndromes Dwarfism Endocrine System Diseases Eye Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications GALC Deficiency GM2 Gangliosidosis Gangliosidoses Gangliosidoses, GM2 Genetic Diseases, Inborn Genetic Diseases, X-Linked Globoid Leukodystrophy H-ABC - Hypomyelination, Atrophy of Basal Ganglia and Cerebellum HBSL HBSL - Hypomyelination, Brain Stem, Spinal Cord, Leg Spasticity HCC - Hypomyelination and Congenital Cataract Hereditary Central Nervous System Demyelinating Diseases Hereditary Sensory and Motor Neuropathy Heredodegenerative Disorders, Nervous System Ichthyosis Immune System Diseases Infant, Newborn, Diseases Infarction Intellectual Disability Intracranial Arterial Diseases Ischemia Joint Diseases Keratosis Kidney Diseases Krabbe Disease LBSL LCC Labrune Syndrome Lacrimal Apparatus Diseases Leukodystrophy, Globoid Cell Leukodystrophy, Hypomyelinating, 5 Leukodystrophy, Hypomyelinating, 6 Leukodystrophy, Metachromatic Leukoencephalopathies Leukoencephalopathy Brain Calcifications and Cysts Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and High Lactate Syndrome (Disorder) Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Liver Diseases Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System MLC1 MLD Male Urogenital Diseases Mct8 (Slc16A2)-Specific Thyroid Hormone Cell Transporter Deficiency Megalencephalic Leukoencephalopathy With Subcortical Cysts Mental Disorders Metabolic Diseases Metabolism, Inborn Errors Metachromatic Leukodystrophy Mouth Diseases Mucinoses Mucopolysaccharidoses Multiple Sulfatase Deficiency Multiple Sulfatase Deficiency Disease Musculoskeletal Diseases Necrosis Nervous System Diseases Nervous System Malformations Neurobehavioral Manifestations Neurodegenerative Diseases Neurodevelopmental Disorders Neurologic Manifestations Neuromuscular Diseases Nutritional and Metabolic Diseases PLP1 Gene Duplication | Blood or Tissue | Mutations PLP1 Null Syndrome PMD Pathologic Processes Pathological Conditions, Signs and Symptoms Pelizaeus Merzbacher Like Disease Pelizaeus-Merzbacher Disease Peripheral Nervous System Diseases Peroxisomal Biogenesis Disorder Peroxisomal Disorders Polyneuropathies Refsum Disease Rheumatic Diseases Salivary Gland Diseases Salla Disease Sialic Acid Storage Disease Sialic Storage Disease Sjogren's Syndrome Sjogren-Larsson Syndrome Sjögren Skin Abnormalities Skin Diseases Skin Diseases, Genetic Skin and Connective Tissue Diseases Sphingolipidoses Stomatognathic Diseases Stroke Sulfatidosis TBCK-Related Intellectual Disability Syndrome TUBB4A-Related Leukodystrophy Urogenital Diseases Urologic Diseases Van Der Knapp Disease Vanishing White Matter Disease Vascular Diseases White Matter Disease X-ALD X-Linked Intellectual Disability X-linked Adrenoleukodystrophy Xanthomatosis Xanthomatosis, Cerebrotendinous Xerostomia Zellweger Syndrome

Sex eligibility

All sexes

Study type

Observational

Primary location

Children's Hospital of Los Angeles, Los Angeles, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

(Affected Subjects):

  • Male or female of any age;
  • Suspected or confirmed diagnosis of leukodystrophy or other disorder affecting the white matter of the brain based primarily on the finding of central nervous system neuroimaging consistent with this diagnosis or on an existing diagnosis of a leukodystrophy or genetic leukoencephalopathy as defined in existing classification systems, or in the presence of variant(s) of uncertain significance or genotype consistent with leukodytrophy;
  • Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent;
  • Willingness to provide clinical data, participate in standardized assessments, and/or provide biologic samples.

Exclusion criteria

(Affected Subjects)

  • Established diagnosis at the time of referral that is not consistent with a genetic disorder of the white matter, such as an acquired demyelinating condition (e.g. multiple sclerosis), or an infectious etiology, with the exception of sequelae of congenital infections such as CMV;
  • Inability to provide consent.

Inclusion criteria

(Healthy Controls)

  • Male or female of any age;
  • Individuals with no confirmed or suspected diagnosis of leukodystrophy or other disorder affecting the white matter of the brain (including affected patients' caregivers);
  • Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent.

Exclusion criteria

(Healthy Controls)

  • Inability to provide consent.

Treatment and study plan

Primary outcomes

  1. Define Novel Homogeneous Groups of Patients with Unclassified Leukodystrophy

    Time frame: 10 years from enrollment

    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.

Secondary outcomes

  1. Assess Validity of Next-Generation Sequencing in the Diagnosis of Leukodystrophies

    Time frame: 10 years from enrollment

    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.

  2. Assess Utility of Next-Generation Sequencing in the Diagnosis of Leukodystrophies

    Time frame: 10 years from enrollment

    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.

  3. Track Current Care of Leukodystrophy Patients

    Time frame: 10 years from enrollment

    Includes a longitudinal collection of clinical data on diagnostic and therapeutic interventions in leukodystrophy patients and related controls.

  4. Track Natural History of Leukodystrophy Patients

    Time frame: 10 years from enrollment

    Includes longitudinal collection of clinical data on disease presentation, progression and morbidities.

  5. Establish Disease Mechanisms in Leukodystrophies

    Time frame: 10 years from enrollment

    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.

  6. Contact for Future Research Studies and/or Clinical Programs

    Time frame: 10 years from enrollment

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Omar S. Sherbini, MPH

CONTACT

[email protected]

215-590-3068

Sponsors and collaborators

Lead sponsor

Children's Hospital of Philadelphia

Other

Collaborators

  • Biogen
  • Boehringer Ingelheim
  • Calliope Joy Foundation
  • Don't Forget Me Foundation
  • Eli Lilly and Company
  • Foundation to Fight H-ABC
  • Ionis Pharmaceuticals, Inc.
  • Myrtelle Inc.
  • National Center for Advancing Translational Sciences (NCATS)
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • National Institutes of Health (NIH)
  • Orchard Therapeutics Ltd.
  • Passage Bio, Inc.
  • Sana Biotechnology
  • Sanofi Winthrop Industrie
  • Synaptix Biotherapeutics Ltd.
  • Takeda
  • United MSD Foundation
  • University of Pennsylvania
  • Yaya Foundation for 4H Leukodystrophy

Registry information

Official study title

The Myelin Disorders Biorepository Project and Global Leukodystrophy Initiative Clinical Trials Network

Acronym: MDBP

Important dates

Study start
2016
Primary completion
2030
Study completion
2030
First posted
Feb 9, 2017
Registry last updated
Oct 23, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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