LeukoSEQ: Whole Genome Sequencing for Unsolved Leukodystrophies

PI: Dr. Adeline Vanderver
Study Location: Children's Hospital of Philadelphia (CHOP)*

LeukoSEQ, a clinical trial launched by Dr. Adeline Vanderver in partnership with Illumina Inc. in November of 2015, is intended for individuals under 18 years of age who have recently identified and unsolved white matter abnormalities. The trial seeks to compare the diagnostic efficacy of CLIA-certified whole genome sequencing (WGS) with standard diagnostic approaches, which currently have a diagnostic success rate of only about 50%.

Eligible candidates must have an index MRI (i.e. first MRI demonstrating white matter abnormalities) performed within two months of study enrollment. Eligible candidates must not have a molecular/genetic diagnosis for the white matter abnormalities, and must not have pending orders or existing results for other genetic testing, including WES, WGS, or iterative panel testing of more than 20 cumulative genes. Enrolled participants will receive results of CLIA-certified WGS, including a separate report on incidental findings, at no cost to them. 

For more information about the trial, or to refer an individual with a recently diagnosed and unsolved white matter disorder, please submit a request via the Contact Us page. You can also find out more about the trial by visiting the ClinicalTrials.gov listing.

*Site visit not required. Open to all candidates living in the United States.


Natural History and Outcome Measures in Alexander Disease

PI: Amy T Waldman, MD, MSCE  
Study Location: Children's Hospital of Philadelphia (Philadelphia, PA)

The purpose of this study is to define the natural history of Alexander Disease, a leukodystrophy that causes neurological dysfunction. Investigators will obtain clinical outcome assessments to measure how the disease affects a patient's gross motor, fine motor, speech and language function, swallowing, and quality of life. The data obtained from this study will be used for the design of future treatment trials.

Participants will be asked to complete physical examinations including physical therapy, occupational therapy, speech and language therapy, and swallowing assessments. Patients (or caretakers) may be asked to complete questionnaires as well. The study asks for participants to return at least once yearly to repeat assessments. For more information about the study, or to refer a study candidate, please contact Geraldine Liu.


Clinical and Genetic Characterization of Leukodystrophies

PI: Genevieve Bernard MD, M.Sc., FRCPC
Study Location: Research Institute of the McGill University Health Center (Montreal, QC)

The purpose of this study is to describe novel disorders and find their causal genes, as well as to better understand leukodystrophies clinically, genetically and pathophysiologically. This is a prospective observational study/bioregistry intended to collect data that will help researchers prepare for therapeutic trials in the leukodystrophy field. 

For more information about the study, or to refer a study candidate, please contact Dr. Bernard.


The Myelin Disorders Bioregistry Project (MDBP)

PI: Adeline Vanderver, MD
Study Location: Children's Hospital of Philadelphia (CHOP)*

The Myelin Disorders Bioregistry Project (MDBP) can be thought of as a "biological database" for leukodystrophies. It was launched over a decade ago by Dr. Adeline Vanderver at Children's National in Washington D.C. and has since moved to its permanent home at the Children's Hospital of Philadelphia (CHOP). The study has enrolled over 1,000 individuals affected with white matter disorders and continues to grow on a weekly basis. Given that white matter disorders are exceedingly rare, the bioregistry has served as central research hub for researchers in the field. Indeed, many of the groundbreaking discoveries that have been made within the field were facilitated by this bioregistry.

The MDBP is open to individuals worldwide affected by leukodystrophies, leukoencephalopathies, or other solved or unsolved white matter abnormalities. Participation requires submission of medical records, MRI images, test results, as well as blood samples from the affected individual and his/her parents. For more information about the project, or to refer an individual affected by a white matter disorder, please submit a request via the Contact Us page.

*Site visit not required for participation. Open to candidates worldwide.


Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD)

PI: Dr. Nancy Braverman
Study Location: Research Institute of the McGill University Health Center*

The Peroxisome Biogenesis Disorders (PBD) are a group of inherited disorders due to defects in peroxisome assembly causing complex developmental and metabolic sequelae. In spite of advancements in peroxisome biology, the pathophysiology remains unknown, the spectrum of phenotypes poorly characterized and the natural history not yet systematically reported. Our aims are to further define this population clinically, biochemically and genetically. The investigators will prospectively follow patients from Canada, the US and internationally, and collect data from medical evaluations, blood, urine and imaging studies that would be performed on a clinical care basis. Patients unable to attend clinics can participate in this study by mailing in their medical information. The investigators will use this information to identify standards of care and improve management.

Participants have the option to be seen in consultation at the McGill University Health Centre in Montreal, Canada, on a yearly basis. This includes a consultation in Genetics, Nutrition, Neurology, and Ophthalmology (OCT and FAF exams). All medical records and images will be collected, retrospectively and prospectively, until the end of the study, and entered anonymously in a database. Molecular testing (through next-generation panel of 75 genes) will be offered to participants whose mutations have not been identified yet. Biospecimens will be collected to identify new biomarkers. Drug screening will be performed on cultured fibroblasts.

Eligible candidates either have a diagnosis of PBD or a single enzyme defect, or are suspected of having this. There are no age restrictions for this study For more information about the study, or to refer an eligible candidate, please contact the study coordinator, Jessie Kulaga-Yoskovitz. You can also find out more about the study by visiting the ClinicalTrials.gov listing.

*Site visit not required. Open to candidates worldwide.


Sjogren-Larsson Syndrome: Natural History, Clinical Variation and Evaluation of Biochemical Markers

PI: William Rizzo, MD
Study Location: University of Nebraska (Omaha, NE)

The study will consist of a clinical component and a scientific component consisting of laboratory investigations of potentially useful biochemical (lipid and protein) markers. Up to 50 Sjogren-Larsson Syndrome (SLS) patients of all ages, gender and ethnic origins will be enrolled. A detailed clinical evaluation will be performed to determine the presence and extent of disease involving the skin, nervous system and eyes. Clinical testing will include brain magnetic resonance imaging (MRI) and spectroscopy (MRS), electroencephalography (EEG), neurocognitive tests, and ophthalmologic examinations. Correlations between clinical abnormalities and laboratory measurements will be tested to identify the most useful biomarkers for future diagnostic and therapeutic studies. To characterize the progression of phenotypic features over time, patients <6 years of age will be followed yearly and patients ≥6 years of age will be followed every 3 years. In addition, a SLS patient registry will be established as a resource for future investigations in SLS.

Eligible candidates must have a genetically or biochemically confirmed diagnosis of Sjogren-Larsson syndrome. Furthermore, they must be able to travel to a STAIR site for periodic follow-up at the intervals described above.

For more information about the trial, or to refer an eligible candidate, please contact Rachel Cooper. You can also find out more about the trial by visiting the ClinicalTrials.gov entry.