February 8, 2015
This image shows the detail of one millimeter of a mouse brain. In green, capillaries that form part of the blood-brain barrier; in red, molecules attached to the shuttle patented by IRB Barcelona have managed to cross the barrier and reach the brain (black background). (Credit: Benjam Oller/IRB Barcelona)
Provided by Snia Armengou, Institute for Research in Biomedicine (IRB Barcelona)
The brain is protected by a barrier of cells that tightly regulates the transport of substances into this organ in order to prevent infection. The essential protective function of this barrier is also a red light for 98% of drug candidates for the treatment of the central nervous system.
Tuesday, inAngewandte Chemie, scientists at the Institute for Research in Biomedicine (IRB Barcelona) presented a shuttle able to cross the blood-brain barrier and transport various substances into the brain. The team of chemists at IRB Barcelona is now studying its application for specific medical conditions. Together with clinical researchers, they are preparing treatments for glioblastoma, the most aggressive brain cancer in adultsFriedreichs Ataxia, a hereditary neurodegenerative disease, and a type of pediatric brain cancer.
It is estimated that 20% of humans at some time will need a treatment that targets the brain, explains Meritxell Teixid, associate researcher at IRB Barcelona and leader of this line of investigation, and for many diseases there are some good candidate drugs but none have the capacity to reach their target and thus there is a subsequent loss of potential. Our shuttle offers a solution to an urgent clinical need. The work has been carried out in IRB Barcelonas Peptides and Proteins Lab. Directed by Ernest Giralt, also senior professor of the UB, this lab is one of the few leading labs worldwide devoted to these kinds of developments.
Open sesame
The blood-brain barrier is not totally hermetic as the brain constantly requires oxygen, iron, insulin, etc. So there are transport mechanisms through doors which open and close continuously. Taking advantage of the receptors through which the brain receives iron, the shuttle-ambulance crosses the barrier without disrupting nutrient flow or altering the protective function of the barrier. We wanted a vehicle that exerted only this function, that was small (a peptide), and that has permanence in blood, says Roger Prades, PhD students and first author of the study, which has taken four years of research into peptide chemistry.
The therapeutic value of the shuttle lies precisely in these two properties, which make it unique, namely its small size, comprising only 12 amino acids, and its permanence in blood from between 12 and 24 hours. Peptides have a half-life in blood of very few minutes. As the peptide is protease-resistant, its therapeutic development feasible, as nobody wants to take a medicine every 5 minutes; furthermore, this peptide could be produced on a large scale. If it were a large molecule, this would be economically complicated, explains Teixid. In preliminary experiments with mice, the study also demonstrates the absence of an immune response and low toxicity.
Medical applications
Read more:
Researchers create 'shuttle' to cross blood-brain barrier