'Trojan horse' crosses blood-brain barrier

The Canadian researchers who published the work claim an iron-transport protein, known as p97, can be used to chaperone a chemotherapeutic agent across the BBB. biOasis Technologies has acquired the technology, which opens up the possibility of delivering therapeutics to the brain for the treatment of neurological disorders, such as metastatic brain tumors. The paper states: "This study demonstrates the unique potential of using p97, as a 'Trojan horse' to ferry normally excluded therapeutic compounds, through the battlements of the BBB, thereby allowing forbidden cargo to traverse from the blood and emerge in the brain​. "New avenues should now be open to explore the generalized use of p97 to transport therapeutic compounds into the brain for the treatment of a variety of chronic and acute CNS diseases​." The approach is said to work by utilising the endogenous receptors possessed by the blood capillaries that compromise the BBB. These receptors ferry an iron transport protein across the BBB, which the researchers used to 'piggyback' therapeutics into the brain. In the research chemotherapeutic agents paclitaxel and adriamycin were covalently linked to p97 and delivered intravenously into mice. Penetration into the brain tissue was tracked using radiolabeled and fluorescent derivatives of the drugs. Without a method of targeting the brain the levels of paclitaxel and adriamycin needed to be effective against tumours can cause cardiotoxicity or neurotoxicity. Consequently, current techniques to deliver chemotherapeutic agents to the brain rely upon the use of highly lipophilic alkylating agents such as nitrosourea and temozolomide, which are able to cross the BBB. However, these therapeutics are largely ineffective against primary tumours. Although the research focused on the delivery of chemotherapeutic agents biOasis envisages the technique being used in the treatment of Parkinson's, Huntingdon's and lysosomal storage diseases. A massive market awaits the company that commercialises a delivery system which traverses the BBB. biOasis faces stiff competition in its pursuit of the 'holy grail', with companies and researchers ploughing a great deal of resources into solving the problem. Nanoparticles have been hailed by some as the panacea in crossing the BBB, with companies such as Midatech hoping to exploit their potential.