WARF: P140126US02

Blood-Brain Barrier Targeting Antibodies to Improve Drug Delivery


Eric Shusta, Angela Jones, Charles Stutz

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing BBB-selective antibodies with enhanced binding specificity.
OVERVIEWEven though therapeutic compounds have been developed for neurologic disorders such as Alzheimer’s disease, these conditions remain difficult to treat in large part because of the blood-brain barrier (BBB). The BBB is a natural defense mechanism that unfortunately interferes with drug delivery, allowing few molecules to enter the brain from the bloodstream. More than 98 percent of small molecule pharmaceuticals and nearly 100 percent of protein and gene therapeutics cannot pass through this barrier.

One promising delivery method involves antibodies that target receptor-mediated systems at the BBB. Drug molecules can be attached to the antibodies and transported into brain tissue. Antibodies that target the transferrin and insulin receptor systems currently are available, but these systems are expressed throughout the body, leading to the mistargeting of expensive pharmaceuticals.

The search continues for new antibodies capable of targeting and/or transporting therapeutic payloads into the brain.
THE INVENTIONUW–Madison researchers have identified a pair of single-chain antibody fragments (scFv15 and scFv38) that may help drugs cross the BBB. The two promising new antibodies are capable of binding antigens expressed at the BBB in vivo.

The researchers panned a human scFv library to identify candidates that specifically bind to brain endothelial cell receptors and may pass through the BBB. Drugs or drug carriers could be attached to these fragments and then transported into the brain.
  • Delivering therapeutics to the brain
  • May lead to new methods of treating disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, autism, multiple sclerosis, brain cancer and stroke
  • Provides a non-invasive method of specifically delivering drugs to the brain
  • Selective and efficient
  • May minimize side effects that can result when drugs are mistargeted
  • Antibody fragments are fully human, lowering the risk of immunogenic reactions that can result when non-human antibodies are used.
STAGE OF DEVELOPMENTThe researchers have identified the two scFv antibody fragments with enhanced binding specificity for the BBB and plan further work in vivo.
Contact Information
For current licensing status, please contact Jennifer Gottwald at or 608-960-9854.
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UW–Madison has the integrative capabilities to complete many key components of the drug development cycle, from discovery through clinical trials. As one of the top research universities in the world, and one of the two best-funded universities for research in the country, UW–Madison offers state-of-the-art facilities unmatched by most public universities.

These include the Small Molecule Screening Facility at the UW Comprehensive Cancer Center; the Zeeh Pharmaceutical Experiment Station, which provides consulting and laboratory services for developing formulations and studying solubility, stability and more; the Waisman Clinical Biomanufacturing Facility; the Wisconsin Institute for Medical Research, which provides UW–Madison with a complete translational research facility; and the innovative, interdisciplinary Wisconsin Institutes for Discovery, home to the private, nonprofit Morgridge Institute for Research and its public twin, WID, part of the university's graduate school. The highly qualified experts at these facilities are ready to work with you to create a library of candidates for drug development.