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.
What did this achievement accomplish?
Dr. Vanderver: The CPIM provided a significant opportunity for GLIA-CTN investigators, patient advocates, and FDA experts to engage in direct scientific dialogue about critical barriers to clinical trial readiness in AGS. The discussion focused on two complementary approaches developed by the consortium: using real-world evidence to strengthen understanding of AGS natural history and developing a patient-centered method for identifying meaningful clinical trial endpoints and outcome assessments. Because CPIMs are specifically designed to allow FDA and external stakeholders to discuss innovative approaches to drug development in a non-binding scientific setting, the meeting provided valuable regulatory perspective at an early stage of development.
How will this impact the rare disease community?
Dr. Vanderver: The impact extends beyond AGS. Rare disease trials frequently face the same challenges: small and heterogeneous patient populations, incomplete natural history data, and difficulty identifying outcome measures that are both clinically meaningful and sensitive to treatment effects. The AGS CPIM demonstrated a framework for addressing these challenges by integrating real-world data with systematic input from patients and families. Importantly, representatives of the AGS Advocacy Association participated in the meeting, helping ensure that the lived experience of individuals and families affected by AGS was represented alongside scientific and regulatory perspectives. This patient-centered approach is consistent with FDA's emphasis on incorporating patients' experiences, priorities, and perspectives into drug development.
How will this advance the goals of your consortium and/or the RDCRN at large?
Dr. Vanderver: The CPIM directly advances GLIA-CTN's goal of moving rare leukodystrophies from natural history characterization toward clinical trial readiness and therapeutic development. For AGS, specifically, regulatory dialogue around natural history evidence and patient-centered endpoints helps clarify the work needed to develop trial designs and outcome measures that are scientifically rigorous, feasible, and meaningful to patients. More broadly, the experience creates a potentially transferable model for other leukodystrophies and RDCRN diseases facing similar trial-readiness challenges. This aligns closely with the RDCRN mission to promote collaborative, multi-site, patient-centered translational and clinical research, and to address unmet trial readiness needs to accelerate development of treatments for rare diseases.