Molecular Trojan horses for blood-brain barrier drug delivery

Abstract

Peptides and recombinant proteins such as neurotrophins, enzymes and monoclonal antibodies, have not been developed as new drugs for the brain because these large molecule drugs do not cross the brain capillary wall, which forms the blood-brain barrier (BBB) in vivo. A new solution to the brain drug delivery problem is the genetic engineering of recombinant fusion proteins. The therapeutic peptide or protein drug is fused to a molecular Trojan horse, which is a second peptide or peptidomimetic monoclonal antibody that binds a specific receptor on the BBB. The Trojan horse enables receptor-mediated delivery of the fusion protein across the BBB so that the protein drug can enter the brain and exert the desired pharmacological effect.