The Stem Cell Podcast

Ep. 93: “Blood Brain Barrier” Featuring Dr. Clive Svendsen

Jun 6, 2017
Dr. Clive Svendsen, a regenerative medicine leader who uses patient-derived iPSCs to model disease and push therapies to clinic. He discusses building blood–brain barrier models, how BBB defects block thyroid hormone entry, endothelial-targeted gene therapy strategies, and using human iPSC systems alongside animal tests to speed translational work.
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INSIGHT

Thyroid Transporter Deficit Is A Blood Brain Barrier Problem

  • MCT8 mutations cause severe neurodevelopmental symptoms because thyroid hormone can't reach the brain, not because neurons lack responsiveness.
  • Clive Svendsen used patient iPSCs to make neurons and a matched blood-brain barrier model showing T3 fails to cross the endothelial layer into neurons.
ADVICE

Treat The Endothelium To Restore Brain Hormone Delivery

  • Targeting endothelial cells can be a practical therapeutic route for brain delivery because the brain vasculature is reachable via the bloodstream.
  • Svendsen suggests AAV delivery into circulation to express MCT8 in brain endothelium so T3 can access neurons.
INSIGHT

Blood Brain Barrier Dysfunction Is A Disease Mechanism

  • Blood-brain barrier dysfunction may underlie diverse neurological diseases beyond drug delivery issues.
  • Svendsen points to Huntington's iPSC studies showing endothelial-specific deficits that alter permeability and could affect disease progression.
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