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.
How are you involved with the RDCRN?
Dr. Porcari: I am the recipient of a career development award through GLIA-CTN, which is affording me protected time to pursue clinical outcome assessment validation and biomarker exploration in TUBB4A-related leukodystrophy. I am also hoping to participate in the Rare Disease Clinical Research Training Program, which will complement my background in epidemiology and clinical research with specialized training in rare disease trial methodology.
How does participating in the network support your long-term development?
Dr. Porcari: Protected time at this stage of my career is essential—it will allow me to gather key preliminary data under expert mentorship and to pursue formative experiences in rare disease research. The network infrastructure and cross-site collaboration have also been instrumental in building a large leukodystrophy natural history study at the Children's Hospital of Philadelphia (CHOP). The TUBB4A-LD cohort alone includes >160 patients, exceedingly large for an ultra-rare disease, and a key prerequisite for this proposal. Meaningfully studying this disorder, as well as rarer hypomyelinating conditions such as GJC2-related leukodystrophy, would not be possible outside this setting. I expect to leverage these data, skills, and collaborations towards a K23 focused on advancing clinical trial readiness in TUBB4A-LD, with a framework ultimately transferable to other hypomyelinating leukodystrophies.