RARE DISEASES CLINICAL RESEARCH NETWORK
Global Leukodystrophy Initiative Clinical Trials Network |  |
A consortium of scientists, industry stakeholders, and patient advocacy leaders working together to promote advances in the diagnosis and treatment of leukodystrophies, a complex, often progressive group of disorders affecting the white matter of the brain due to the loss or absence of myelin, the protective coating around nerves. | |
Principal Investigators
Children's Hospital of Philadelphia
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TOP PUBLICATION
JOURNAL: Neurology
X-linked adrenoleukodystrophy (ALD) is a genetic disorder characterized by the disruption in fat metabolism (break down) which leads to the accumulation of long-chain fatty acids throughout the nervous system, adrenal glands, and testes. Newborn screening has enabled the widespread use of brain MRI scans for early detection and treatment of cerebral ALD (cALD). However, it can be challenging to differentiate early cALD lesions (pathologic, or disease-related) from incidental findings (non-disease-related).
In this study, researchers characterized features of incidental MRI findings in cALD. The team analyzed 390 MRI reports from 69 boys with ALD.
Results show that incidental findings were commonly reported during cALD surveillance. These incidental findings were distinguishable from true cALD lesions based on anatomic location, stability over time, and persistent absence of contrast enhancement. Authors note that these findings provide a practical framework for differentiating incidental findings from cALD lesions during surveillance.
What was your consortium's most significant achievement from the past year?
Adeline Vanderver, MD, Principal Investigator, GLIA-CTN: The Critical Path Innovation Meeting (CPIM) for Aicardi-Goutières Syndrome (AGS) took place on November 17, 2025. GLIA-CTN leveraged two of its core initiatives—a real-world, evidence-based approach to natural history studies and a novel method for identifying patient-centered clinical trial endpoints and outcome assessments for AGS—in alignment with the FDA’s 2022 guidance on Patient-Focused Drug Development, to conduct a successful meeting with the FDA. This was done in close collaboration with patient advocacy leaders within the AGS space.
EARLY CAREER INVESTIGATOR SPOTLIGHT
What are your research goals?
Dr. Porcari: My overarching career goal as a clinician-scientist is to improve care for children with leukodystrophies by advancing disease-modifying therapies. Once considered untreatable, several leukodystrophies now have FDA-approved therapies or active clinical trials, yet for many others, preclinical advances have outpaced the natural history work needed to design effective trials. This is particularly true for the hypomyelinating leukodystrophies, a growing group of >15 disorders with overlapping features of motor delay, slow regression, and deficient brain myelination, which largely lack validated outcome measures and biomarkers for clinical trials. My research focuses on closing these gaps in TUBB4A-related leukodystrophy by validating patient-centered clinical outcome assessments and characterizing neurophysiological biomarkers, aiming to ultimately build a clinical trial readiness framework transferable across hypomyelinating conditions.