Novel endothelial-specific molecules (ESMs) actively cross BBB and carry other molecules with them

• The Problem: Brain and retina are shielded to prevent entry of infectious agents and toxins and maintain ionic homeostasis. >98% of small molecules and macromolecules are prevented from crossing the BBB and BRB. Drugs that cross BBB are limited to small lipophilic molecules. Larger hydrophilic molecules do not cross BBB/BRB. We created a library of tens of small molecule ESMs with exquisite specificity and efficiency for entering blood endothelial cells and tested them in vivo.
• Our solution: ESMs are inherently fluorescent and can be tracked in vivo (Fig1)
• ESMs cross BBB through SLC membrane transporters, reach endothelial cytosol and nucleus, when administered topically (Fig 2) and I.V. (not shown)
• ESMs can be conjugated to molecules up to 1000 Da (testing of large molecules under way) without loss of BBB-crossing properties and endothelial specificity and serve as molecular trojan hoses to transport drug across the BBB (Fig 3).
• Lead Innovator: Jaime Grutzendler, M.D.
• IP Status: PRV application filed in 2018