The Myelin Disorders Biorepository Project

a study on Leukodystrophy White Matter Disease Leukoencephalopathies 4H Syndrome Adrenoleukodystrophy AMN ALD Gene Mutation Adrenomyeloneuropathy Aicardi Goutieres Syndrome AGS Alexander Disease Alexanders Leukodystrophy AxD ADLD Canavan Disease CTX Cerebrotendinous Xanthomatoses Krabbe Disease GALC Deficiency Globoid Leukodystrophy TUBB4A-Related Leukodystrophy HBSL LBSL ALSP CSF1R Gene Mutation Cataracts Liver Cancer MLC1 MLD Metachromatic Leukodystrophy Pelizaeus-Merzbacher Disease PLP1 Null Syndrome Peroxisomal Biogenesis Disorder Zellweger Syndrome Refsum Disease Salla Disease Sialic Storage Disease Sjögren Sjögren-Larsson Syndrome Van Der Knapp Disease Vanishing White Matter Disease Charcot-Marie-Tooth Disease Allan-Herndon-Dudley Syndrome CADASIL Cockayne Syndrome Multiple Sulfatase Deficiency Gangliosidoses GM2 Gangliosidosis BPAN Labrune Syndrome LCC Mucopolysaccharidosis TBCK-Related Intellectual Disability Syndrome Sjögren Syndrome Neuropathy Tay-Sachs Disease Cerebrotendinous Xanthomatosis

Location: at San Diego, California and other locations
Dates: study started December 2016
completion around December 2030

Description

Summary

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.

Official Title

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

Details

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.

Keywords

Leukodystrophy, White Matter Disease, Leukoencephalopathies, 4H Syndrome, Adrenoleukodystrophy, AMN, ALD, ALD Gene Mutation, ALD (Adrenoleukodystrophy), X-linked Adrenoleukodystrophy, X-ALD, Adrenomyeloneuropathy, Aicardi Goutieres Syndrome, AGS, Alexander Disease, Alexanders Leukodystrophy, AxD, ADLD, Canavan Disease, CTX, Cerebrotendinous Xanthomatoses, Krabbe Disease, GALC Deficiency, Globoid Leukodystrophy, TUBB4A-Related Leukodystrophy, H-ABC - Hypomyelination, Atrophy of Basal Ganglia and Cerebellum, HBSL, HBSL - Hypomyelination, Brain Stem, Spinal Cord, Leg Spasticity, LBSL, Leukoencephalopathy With Brain Stem and Spinal Cord Involvement and High Lactate Syndrome (Disorder), Leukoencephalopathy With Brainstem and Spinal Cord Involvement and Lactate Elevation, ALSP, CSF1R Gene Mutation, HCC - Hypomyelination and Congenital Cataract, MLC1, Megalencephalic Leukoencephalopathy With Subcortical Cysts, MLD, Metachromatic Leukodystrophy, PMD, Pelizaeus-Merzbacher Disease, PLP1 Null Syndrome, PLP1 Gene Duplication &#X7C; Blood or Tissue &#X7C; Mutations, Pelizaeus Merzbacher Like Disease, Peroxisomal Biogenesis Disorder, Zellweger Syndrome, Refsum Disease, Salla Disease, Sialic Storage Disease, Sjögren, Sjogren-Larsson Syndrome, Van Der Knapp Disease, Vanishing White Matter Disease, Charcot-Marie-Tooth, CMT, Mct8 (Slc16A2)-Specific Thyroid Hormone Cell Transporter Deficiency, Allan-Herndon-Dudley Syndrome, Cadasil, Cockayne Syndrome, Multiple Sulfatase Deficiency, Gangliosidoses, GM2 Gangliosidosis, BPAN, Labrune Syndrome, LCC, Mucopolysaccharidoses, TBCK-Related Intellectual Disability Syndrome, leukoencephalopathy, myelin, demyelinating, mdbp, Sjogren's Syndrome, Intellectual Disability, Charcot-Marie-Tooth Disease, Nerve Compression Syndromes, Hereditary Sensory and Motor Neuropathy, GM2 Gangliosidoses, Tay-Sachs Disease, Globoid Cell Leukodystrophy, Multiple Sulfatase Deficiency Disease, Sialic Acid Storage Disease, Cerebrotendinous Xanthomatosis, Peroxisomal Disorders, Xanthomatosis, Syndrome

Eligibility

You can join if…

(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;
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.

You CAN'T join if...

(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;
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.

Locations

University of California, San Diego (Rady Children's Hospital) accepting new patients
San Diego California 92123 United States
Children's Hospital of Orange County accepting new patients
Orange California 92868 United States

Details

Status: accepting new patients
Start Date: December 2016
Completion Date: December 2030 (estimated)
Sponsor: Children's Hospital of Philadelphia
ID: NCT03047369
Study Type: Observational [Patient Registry]
Participants: Expecting 12000 study participants
Last Updated: November 2024

I’m interested in this study!