Where Does Your Drug Go? Brain-Wide Biodistribution and Target Engagement with LS-Journey™

In Episode 2 of the Vibraint Product Series, Harry Salt is back with Jacob Hecksher-Sørensen — CEO and Co-founder of Vibraint — to explore one of the most powerful and underutilised applications of whole brain light sheet imaging: drug biodistribution and target engagement mapping. Jacob shares the origin story of this technique at Vibraint — starting with fluorescent GLP-1 mapping in mouse brains over 15 years ago — and explains how that same approach has since been used to study semaglutide, brain shuttles, RNA/DNA therapeutics, and AAV vectors. He also reveals that the GLP-1 brain distribution data generated by his team at Novo Nordisk was used in the NDA submission that qualified Saxenda as the first approved obesity drug. In this episode: 00:16 — The origin story: the first fluorescent GLP-1 brain map, 15 years ago 02:59 — How drug distribution is quantified: fluorescent intensity across 800+ brain regions 03:17 — Controls and study design: knockout animals, competitive displacement, and PBS baselines 04:48 — Which drug types work best: peptides, antibodies, and RNA/DNA molecules 09:36 — Gene therapy and AAV biodistribution — an emerging frontier 10:33 — The blood-brain barrier: circumventricular organs, brain shuttles, and how they transform CNS drug delivery 12:26 — The piggybacking hypothesis: how fatty acid-conjugated peptides may access unexpected brain regions 13:36 — Target engagement: receptor co-registration, knockout controls, downstream phosphorylation, and Alzheimer's antibody binding 15:55 — How biodistribution data accelerates drug discovery and enables early programme kills 17:31 — Real-world applications: GLP-1 drugs, semaglutide ozempic, wegovy, tirzepatide, zepbound, brain shuttles, and AAV 19:09 — What data you receive: statistical brain maps, per-region intensity, CNS-Voyager™ delivery 21:20 — The Saxenda NDA: how this data has already been used in a regulatory submission 22:00 — Compound selection and decision making: comparing five candidates head-to-head 23:34 — How this compares to PET imaging — complementary, not competing 24:58 — Chronic studies: receptor downregulation and how distribution changes over time About Vibraint Vibraint (Virtual Brain Technologies) is a Copenhagen-based preclinical CRO specialising in quantitative whole brain imaging for academic neuroscience, biotech, and pharma. LS-Journey™ delivers brain-wide fluorescent drug distribution maps registered to a peer-reviewed CCF across 800+ anatomical regions, delivered interactively via CNS-Voyager™. vibraint.dk [email protected] #DrugBiodistribution #BrainImaging #TargetEngagement #BloodBrainBarrier #LightSheetMicroscopy #GLP1 #Semaglutide #BrainShuttle #CNSDrugDiscovery #LSJourney #Vibraint #Preclinical #AAV #GenTherapy #ozempic, #zepbound, #wegovy #tirzepatide #semaglutide