Leukodystrophy Center: Programmatic Highlights and Initiatives

The Leukodystrophy Center at Children’s Hospital of Philadelphia provides comprehensive clinical care, diagnostic testing, and the most advanced treatments available to infants, children and adolescents with inherited white matter diseases. Since our inception in 2016, we have had a nearly five-fold increase in patient visits and attracted more than three times as many affected individuals. Approximately 40% of affected individuals travel from outside the tri-state area to consult with our experts.

Our program begins with accurate and prompt diagnosis, including use of the most comprehensive genetic testing available. For children and adolescents who are already living with the complex challenges of established leukodystrophies, we provide multidisciplinary, state-of the-art care.

Our clinic is characterized by a multidisciplinary clinical approach that includes neurologists, geneticists, physiatry, complex care pediatrics, speech pathology, nutrition, physical therapy, occupational therapy and social work. Together, this team is able to provide a comprehensive care approach for the multisystemic involvement seen in individuals affected by leukodystrophy.

We pursue research that leads to clinical trials, new treatments, and potential cures. Our goal is to create standardized methods of treatment for leukodystrophy, including personalized genetic medicine, repurposing strategies, and bone marrow and stem cell transplantation. For newborns identified through neonatal screening as being at risk of having leukodystrophy, and for children diagnosed prior to the onset of symptoms, we deliver potentially curative therapies.

Big news for leukodystrophy patients and families! The U.S. Food and Drug Administration recently granted accelerated approval for a personalized gene therapy for cerebral adrenoleukodystrophy (CALD). Our Leukodystrophy Center is excited to offer this new therapy to qualifying patients. Learn more here.

Programmatic highlights and initiatives

The Leukodystrophy Center includes several disease specific clinical trials, including antisense oligonucleotide therapies in Alexander disease, immune modulation and reverse transcriptase inhibitors in Aicardi Goutières Syndrome, intrathecal enzyme replacement in Metachromatic Leukodystrophy, and gene therapy in Krabbe disease. These investigational therapies, in previously untreatable disorders, offer new hope to this disease community.

In addition, we offer new levels of standards of clinical care to children with specific disorders, such as Aicardi Goutières Syndrome now treatable with Janus Kinase Inhibitors, and a comprehensive newborn screening follow- up program for children diagnosed at birth with X-linked Adrenoleukodystrophy.

Finally, we are committed to the accurate and timely diagnosis of all children and adults affected by leukodystrophy. Observational studies in the Center suggest that 1 in 5 children affected by a leukodystrophy receive a disease targeted intervention once accurately diagnosed, and almost all diagnosed children receive key disease monitoring. For this reason, we offer advanced genetic testing, including whole genome sequencing.

Through CHOP Open, we host web-based educational sessions for medical providers in leukodystrophy diagnosis and care, as well as complex care management of leukodystrophy associated symptoms. We also have patient directed outreach, and in the past years have hosted patient-facing conferences in Aicardi Goutières Syndrome, Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum, and Pelizaeus Merzbacher disease.

We are also committed to training the next generation of leukodystrophy providers. We host the P3 program in translational therapeutics for students in between undergraduate and graduate studies with the Institute of Translational Medicine at the University of Pennsylvania. We also partner with the Rare Disease Clinical Research Network at the National Institutes of Health (NIH) to offer career development awards to future leaders in leukodystrophy research and clinical care.

Current research

The Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) is an NIH funded consortium of scientists, industry stakeholders, and patient advocacy leaders working together to promote advances in the diagnosis and treatment of leukodystrophies. Our shared research infrastructure supports collection and analysis of robust clinical data and biological specimens to pave the way for transformative therapeutic trials across the leukodystrophies. Data from the GLIA-CTN currently supports clinical trials in Metachromatic Leukodystrophy, Adrenoleukodystrophy, Alexander disease and Aicardi Goutieres Syndrome.
Our ongoing and upcoming studies and trials include:

  • A Study to Evaluate the Safety and Efficacy of ION373 in Patients With Alexander Disease (AxD); NCT04849741
  • Study of Safety, Tolerability and Efficacy of PBKR03 in Pediatric Subjects With Early Infantile Krabbe Disease (GALax-C); NCT04771416
  • A Study of Intrathecal SHP611 in Participants With Late Infantile Metachromatic Leukodystrophy (Embolden); NCT03771898
  • JAK Inhibitor Treatment in Aicardi Goutieres Syndrome; NCT03921554
  • Reverse Transcriptase Inhibitors in Aicardi Goutières Syndrome (RTI in AGS); NCT03304717
  • The Myelin Disorders Biorepository Project (MDBP); NCT03047369
  • LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies; NCT02699190