Characterisation of peptides specific for receptor/transport systems of the
blood brain barrier, as lead molecules for the development of drug delivery
vectors
Marion David, Yves Molino, Aude Fortoul, Patrick Vlieghe and Michel Khrestchatisky
Neurobiologie des Interactions Cellulaires et Neurophysiopathologie (NICN), UMR 6184,
CNRS-Université Aix Marseille II, IFR Jean Roche ; VECT-HORUS S.A.S. Marseille,
France.
While CNS (brain and spinal cord) diseases are the world’s leading cause of disability and
account for more hospitalisations and sustained care than almost all other diseases combined,
many existing drugs as well as drugs currently in development are rendered ineffective in
treating CNS diseases due to scientists’ inability to effectively deliver and sustain them in the
CNS. Indeed, the major problem in drug delivery from blood vessels to the CNS is the high
impermeability of these blood vessels that form the “blood brain barrier” (BBB).
Our global objective is the development of collections of vectors dedicated to enhancing drug
delivery to the diseased CNS. Vectors can also find applications in other fields, both
therapeutic and diagnostic, and in particular in oncology and brain imaging. We have set up a
technological platform combining biotechnological processes and biomolecular chemistry for
high throughput screening (HTS) of peptide libraries on cloned receptors or transporters
involved in trans-cellular transport across the BBB and on stable cell lines expressing these
receptors, for the characterization of receptor-specific peptides. We have now characterised
peptides of interest which conjugated to different tracer molecules bind to the targeted
receptors and undergo endocytosis. We are currently characterising the potential of these
peptides to cross the BBB, using in vitro models of the BBB and in vivo administration.