Descripción del proyecto
Administración de fármacos al cerebro: ingeniería de un nuevo transportador cerebral
La barrera hematoencefálica (BHE) dificulta la administración de fármacos en el cerebro, lo que limita las opciones de tratamiento de enfermedades como el cáncer o los trastornos neurodegenerativos. Los métodos actuales de administración de fármacos a través de la BHE carecen de un transporte eficaz y una captación tisular periférica, lo cual reduce el índice terapéutico de los fármacos destinados al cerebro. El equipo del proyecto OBGate, financiado por el Consejo Europeo de Investigación, se propone crear un nuevo receptor ortogonal capaz de transportar eficazmente fármacos a través de la BHE y que únicamente se exprese en el endotelio cerebral. Los investigadores diseñarán un nuevo transportador de BHE y lo administrarán mediante un nanotransportador que imita la forma en que los virus entran en las células. Este enfoque puede revolucionar el transporte cerebral y mejorar las opciones terapéuticas de las enfermedades neurológicas.
Objetivo
Many impairing illnesses raging from metastatic cancers to neurodegenerative diseases affect the brain. Unfortunately, delivery of therapeutics to the brain is highly challenging due to the blood-brain barrier (BBB). Despite decades of research, no safe and efficient strategy to overcome this barrier has reached clinical application. Here we propose a concept that will revolutionize brain transport: creating a new orthogonal receptor to mediate transport across the BBB. Numerous molecules have been developed to achieve brain delivery via receptor-mediated transport. However, delivery is very limited presumably because no receptor combines 3 key features: high transport efficiency, high expression on the BBB, and low expression on peripheral tissues. This results into peripheral tissues acting as a sink and dramatically lowering the therapeutic index of drugs aimed for the brain. The greatest limitation of current efforts is trying to solve both selectivity and efficient transport in a single delivery vehicle. Our unprecedented approach is based on dissecting this problem in two: increasing transport efficiency with the new orthogonal receptor OBGate and addressing selectivity with a highly efficient targeted vehicle to express the receptor only at the BBB. Since this receptor will not bind any endogenous ligand, its properties and intercellular trafficking can be engineered with minimal alteration of brain homeostasis. This will enable to unravel the key determinants of BBB transport and to build an ideal transport system. Selective expression of this receptor in the brain endothelium will be achieved by engineering a gene delivery nanocarrier mimicking the two-stage viral entry into BBB cells. As an example to prove the efficiency of our system we will aim to deliver biotherapeutics for the treatment of brain metastatic breast cancer. Overall, we will open a new gate to the brain that is poised to be paradigm-breaking in the treatment of neurological diseases.
Ámbito científico
Palabras clave
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
ERC - Support for frontier research (ERC)Institución de acogida
08017 Barcelona
España