Rare Disease Day 2026 | From Odyssey to Innovation, A Rare Journey to N of 1 Trial

Why It Matters

The story demonstrates how patient‑led advocacy can convert a solitary rare‑disease case into a fully funded N‑of‑1 trial, offering a scalable blueprint for accelerating therapies and redefining the role of academic medicine in ultra‑rare disease research.

Key Takeaways

• Caregiver advocacy secured a personalized N-of-1 trial for APBD.
• Johns Hopkins leveraged multidisciplinary team to accelerate rare‑disease research.
• Nonprofit N‑Laurum partnered to develop antisense‑oligo therapy for APBD.
• Active patient involvement essential for trial design and data collection.
• Advocacy adds a fourth pillar—policy influence—to academic medicine.

Summary

Rare Disease Day 2026 highlighted a deeply personal yet broadly instructive case: the journey of Heidi, a patient with adult polyglucosan body disease (APBD), from a prolonged diagnostic odyssey to the launch of an N‑of‑1 clinical trial. The session brought together Johns Hopkins genetic counselors, neurologists, psychiatrists, and researchers from the Applied Physics Laboratory, illustrating how a caregiver’s relentless advocacy can align nonprofit developers, academic physicians, and research institutes around a single patient’s needs. The discussion underscored several critical insights. APBD affects only a few hundred individuals worldwide, and Heidi’s variant carries a rare deep‑andronic mutation. After eight years of uncertainty, the NIH Undiagnosed Diseases Program finally identified the condition in 2018. A partnership with the nonprofit N‑Laurum, which focuses on antisense‑oligo (ASO) therapies, enabled a proposal for a bespoke trial. Johns Hopkins provided a multidisciplinary team—including neurology, pain management, psychiatry, and advanced MRI research—to support daily low‑carbohydrate diets, intensive physiotherapy, and round‑the‑clock caregiving, while also contributing natural‑history data to shape the trial protocol. Notable moments included Rob Shrier’s assertion that “advocacy is medicine,” and Dr. Justin MacArthur’s description of himself as Heidi’s “quarterback doctor,” emphasizing the necessity of a single point of clinical leadership. The speakers highlighted concrete actions: participation in Duke’s natural‑history study, collaboration with the Kennedy Krieger Institute on quantitative MRI, and the creation of a legal framework linking Hopkins, KKI, and N‑Laurum. The broader implication is a replicable model for ultra‑rare diseases: caregiver‑driven advocacy can catalyze institutional collaboration, accelerate trial design, and embed advocacy as a fourth pillar of academic medicine alongside care, research, and education. This approach promises faster access to experimental therapies and may reshape funding and regulatory pathways for similarly rare conditions.

Original Description

This panel will highlight one rare case, starting with a diagnostic odyssey, holistic care, and progress toward an N-of-1 trial. Together, the panelists (Dr. Mallack, Dr. McArthur, Dr. Speed, and Rob Schrier) will explore how scientific discovery and compassionate multidisciplinary care intersect—and how collaboration between patients, families, and clinicians drives progress in rare disease research and management. #rarediseaseday #johnshopkins