ABSTRACT Leukodystrophies are inherited diseases that affect the white matter of the brain due to the loss or absence of myelin, the lipid membrane that insulates axons in the nervous systems. The leukodystrophy community is at a key turning point. Novel molecular approaches have increased disease recognition. At the same time key disorders now have potential treatment pathways. There is urgent unmet need in clinical trial readiness, lest the promise in pre-clinical development be unable to be translated to well-designed clinical trials. This gap in knowledge has galvanized stakeholders in the disease community. In collaboration with advocacy partners, we have formed a research-based consortium, the Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN) that is focused on, but not limited, to a core set of ten leukodystrophies that are at or approaching stages of clinical trial readiness. Approaches will include Clinical Outcome Assessments (COA) and Patient Reported Outcomes (PRO) with a focus on reliability, reproducibility and validity. Additionally, we will expand advanced methodologies for Electronic Medical Record (EMR) extraction of natural history data for the leukodystrophies. Oversight for these projects will occur under a well-developed Administrative Unit at the Children’s Hospital of Philadelphia (CHOP), which includes the GLIA-CTN Data Integration Core staffed by bioinformatics, epidemiologists, and biostatisticians. All aspects of the program are carefully aligned with our patient advocacy partners, represented by the Chair and Co-Chair of the GLIA-CTN Patient Advocacy Committee, who have provided meaningful input and will be stakeholders in data sharing platforms. Together, these approaches will expand our clinical trial readiness platform across the leukodystrophies, enabling transformation of the field.