Brain shuttles and mouse models: Enabling brain-targeted drug development through non-exclusive licensing
Brain Shuttles to TfR and CD98hc are available for licensing to sponsors
Our antibody-fragment-based brain transport shuttles bind to proteins on the capillary side of human brain microvascular endothelial cells (BMECs), are transported through these cells, and are then released from the brain side of the capillaries, thereby efficiently crossing the blood brain barrier (BBB). We have discovered and are developing three different panels of shuttles composed of antibody fragments. Each panel includes several carefully selected antibodies that bind to a distinct BMEC surface protein transport target: transferrin receptor (TfR), CD98 heavy chain (CD98hc), or an undisclosed 3rd target. Brain shuttles in each of these three panels increase brain uptake of the tested drugs by 10- to 60-fold compared to the same drugs without a shuttle. The shuttles can be used to deliver therapeutic antibodies, oligonucleotides, enzymes, and other therapeutic or diagnostic payloads. They are available for non-exclusive licensing to program sponsors.
Brain transport models for TfR, CD98hc, and Target 3 are available for licensing
For each panel of shuttles binding a distinct transport target, we have generated a humanized mouse line in which the extracellular domain of the mouse protein is replaced with the human extracellular domain. These extensively characterized mouse lines, which currently are widely used in multiple labs throughout industry and academia, allow shuttles that bind to the human transport protein to be tested and pre-clinically validated in mice. They can be bred with disease models to create combined brain transport and brain disease models.
Brain shuttle pre-competitive research sponsorship: Multiple companies together supporting discovery of new brain shuttles
Our first pre-competitive project supports the discovery of diverse brain-targeting shuttles and specially engineered mouse models in which drugs of interest fused to these brain shuttles can be tested. This research can benefit each sponsor’s drug programs. The program is focused on helping to identify best practices in brain shuttle discovery and on making newly discovered shuttles available for the development of innovative brain-targeted therapeutics. Pre-competitive sponsors have jointly supported the discovery of shuttle panels binding the Transferring Receptor (TfR) and CD98 heavy chain (CD98hc) proteins, and of a 3rd undisclosed target, along with the discovery and validation of new transport targets and shuttles. Sponsors receive multiple benefits for their brain therapeutic programs, including the opportunity to license non-exclusively the brain shuttle compounds emerging from the sponsored research.
The complexity of this problem makes it challenging for individual research institutions or companies to solve on their own. This collaboration offers a compelling opportunity to discover new approaches for drug delivery to the brain.
Industry Sponsors
- Alnylam Pharmaceuticals
- Bristol-Myers Squibb Co. (BMS)
- Eisai, Inc. (past)
- Eli Lilly and Co.
- Lundbeck A/S
- Merck (Merck, Sharpe and Dohme, LLC)
- Visterra (owned by Ostuka Pharmaceuticals)
Antibody and Target Discovery Partners
- Cell Signaling Technologies, Inc.
- FairJourney Biologics
- Lundbeck A/S
Government Granting Agencies
- Massachusetts Life Sciences Center
- United States Department of Defense