Compounds for Drug Delivery Across Blood-Brain Barrier
Diseases in the brain are difficult to treat. These include cancer metastasis to the brain (such as lung cancer, breast cancer, etc), ischemic stroke, Alzheimer's disease, and Parkinson's disease. The main reason of treatment failure is because the brain is protected by the blood-brain barrier (BBB), and most drugs cannot cross the BBB to enter the brain. Various methods have been tried to cross the BBB, but success is minimal. The transferrin receptor is expressed in the endothelium of the brain and antibodies have been developed to bind to transferrin receptor and shuttle drugs into the brain. However, antibodies are limited by their large size (~150 kd) and associated toxicities. Using an on-bead two-color (OBTC) combinatorial cell-screening technology, we discovered a
new compound that binds to the transferrin receptor and crosses BBB into the brain in mice studies. The compound is named TRBP6. It is a peptoid (oligo-N-substituted glycine) which closely resembles peptide except that the side chain extends from the main chain nitrogen rather than from the α-carbon. It is protease-resistant and highly tissue permeable, and is non-immunogenic. We are in the process of optimizing the structure of TRBP6 and hope to develop more potent derivatives of the compound. TRBP6 and related compounds can form the basis of potential drugs for
the treatment of a variety of diseases. For example, they can be linked to an anti-cancer drug to deliver the drug cross BBB to treat metastatic cancers in the brain. Alternatively, they can be linked to a neuroprotective agent to deliver the drug into the brain to treat ischemic stroke, Alzheimer's disease, and Parkinson's disease.