The Myelin Disorders Biorepository Project (MDBP)

October 22, 2025 updated by: Adeline Vanderver, MD, Children's Hospital of Philadelphia

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

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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Estimated)

12000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital of Los Angeles
        • Contact:
          • Jonathan Santoro, MD
      • Orange, California, United States, 92868
        • Recruiting
        • Children's Hospital of Orange County
        • Contact:
          • Changrui Xiao, MD
      • Palo Alto, California, United States, 94304
        • Recruiting
        • Stanford University (Lucile Packard Children's Hospital)
        • Contact:
          • Keith Van Haren, MD
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California, Davis (UC Davis Health)
        • Contact:
          • William Benko, MD
      • San Diego, California, United States, 92123
        • Recruiting
        • University of California, San Diego (Rady Children's Hospital)
        • Contact:
          • Jennifer Yang, MD
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Benioff Children's Hospital
        • Contact:
          • Alexander Fay, MD, PhD
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Recruiting
        • Children's National Medical Center
        • Contact:
          • Jamie Fraser, MD, PhD
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Emory University (Children's Healthcare of Atlanta)
        • Contact:
          • Stephanie Keller, MD
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann & Robert H. Lurie Children's Hospital of Chicago
        • Contact:
          • Jennifer P Rubin, MD
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Kennedy Krieger Institute
        • Contact:
          • Ali Fatemi, MD, MBA
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital (MGH)
        • Contact:
          • Florian Eichler, MD
    • Minnesota
      • Minneapolis, Minnesota, United States, 55454
        • Recruiting
        • University of Minnesota
        • Contact:
          • Paul Orchard, MD
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
        • Contact:
          • Radhika Dhamija, MBBS
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Atrium Health Wake Forest Baptist
        • Contact:
          • Jennifer Harmon, MD, PhD
    • Ohio
      • Akron, Ohio, United States, 44308
        • Recruiting
        • Akron Children's Hospital
        • Contact:
          • Matthew Ginsberg, MD
      • Columbus, Ohio, United States, 43205
        • Recruiting
        • Nationwide Children's Hospital
        • Contact:
          • Margie Ream, MD, PhD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania
        • Contact:
          • Jennifer Orthmann-Murphy, MD, PhD
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • The Children's Hospital of Philadelphia
        • Sub-Investigator:
          • Laura Adang, MD, PhD, MSTR
        • Sub-Investigator:
          • Amy Waldman, MD, MSCE
        • Contact:
        • Principal Investigator:
          • Adeline Vanderver, MD
      • Pittsburgh, Pennsylvania, United States, 15219
        • Recruiting
        • University of Pittsburgh Medical Center
        • Contact:
          • Deepa Rajan, MD
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine (Texas Children's Hospital)
        • Contact:
          • Lisa Emrick, MD
      • Houston, Texas, United States
        • Recruiting
        • UT Health Houston
        • Contact:
          • Mary Kay Koenig, MD
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah (Primary Children's Hospital)
        • Contact:
          • Joshua Bonkowsky, MD, PhD
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Contact:
          • Emily Shelkowitz, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
10 years from enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
10 years from enrollment
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.
10 years from enrollment
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.
10 years from enrollment
Track Natural History of Leukodystrophy Patients
Time Frame: 10 years from enrollment
Includes longitudinal collection of clinical data on disease presentation, progression and morbidities.
10 years from enrollment
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.
10 years from enrollment
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.
10 years from enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Hospital of Philadelphia

Collaborators

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

Investigators

  • Principal Investigator: Adeline Vanderver, MD, Children's Hospital of Philadelphia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 8, 2016

Primary Completion (Estimated)

December 8, 2030

Study Completion (Estimated)

December 8, 2030

Study Registration Dates

First Submitted

February 1, 2017

First Submitted That Met QC Criteria

February 8, 2017

First Posted (Estimated)

February 9, 2017

Study Record Updates

Last Update Posted (Estimated)

October 23, 2025

Last Update Submitted That Met QC Criteria

October 22, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-011236
  • U54NS115052 (U.S. NIH Grant/Contract)
  • U01NS106845 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing Time Frame

IPD may be shared at any time.

IPD Sharing Access Criteria

Only aggregate data will be shared publicly. Please contact a member of the central study team for information regarding the release of IPD.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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