EP 244: Building the first n-of-1 ASO: The new frontier of rare disease with Timothy Yu of Boston Children’s Hospital

This week on The Genetics Podcast, Patrick is joined by Dr. Timothy Yu, Associate Professor of Pediatrics at Harvard Medical School and Physician/Researcher at Boston Children’s Hospital. They discuss how one child’s hidden genetic mutation led Tim into individualized ASO medicine, what it takes to develop n-of-1 therapies, and how new regulatory frameworks could expand treatment options for children with ultra-rare genetic disease.

Show Notes

0:00 Intro to The Genetics Podcast

01:00 Welcome to Tim

02:05 How uncovering the genetic mutation underlying an ultra-rare disease led Tim into personalized ASO medicine

07:38 Challenges in developing a custom ASO 

12:25 How Tim’s team has scaled individualized ASO therapies to reach more than 50 patients worldwide

16:18 Measuring clinical benefit in n-of-1 therapies with natural history data, wearables, and biomarkers

20:24 How the N-of-1 Collaborative helps rare disease researchers share infrastructure 

24:28 Comparing ASOs, base editing, and prime editing for individualized rare disease therapies

30:06 Finding scalable models for n-of-1 therapies in newborn genetic disease

33:52 The potential impact of the FDA’s Plausible Mechanism framework on bespoke therapies

36:58 Connecting rapid newborn genome sequencing to earlier treatment for rare genetic disease

42:10 Closing remarks