• Open Access

Transport characteristics of a novel peptide platform for CNS therapeutics


Correspondence to: Richard BÉLIVEAU,
Laboratoire de Médecine Moléculaire,
Université du Québec à Montréal,
CP 8888, succursale Centre-Ville,
Montréal H3C 3P8, Canada.
Tel.: 514-987-3000-X6697
Fax: 514-987-0246
E-mail: oncomol@nobel.si.uqam.ca


New and effective therapeutics that cross the blood-brain barrier (BBB) are critically needed for treatment of many brain diseases. We characterize here a novel drug development platform that is broadly applicable for the development of new therapeutics with increased brain penetration. The platform is based on the Angiopep-2 peptide, a sequence derived from ligands that bind to low-density lipoprotein receptor-related protein-1 (LRP-1), a receptor expressed on the BBB. Fluorescent imaging studies of a Cy5.5Angiopep-2 conjugate and immunohistochemical studies of injected Angiopep-2 in mice demonstrated efficient transport across the BBB into brain parenchyma and subsequent co-localization with the neuronal nuclei-selective marker NeuN and the glial marker glial fibrillary acidic protein (GFAP). Uptake of [125I]-Angiopep-2 into brain endothelial cells occurred by a saturable mechanism involving LRP-1. The primary sequence and charge of Angiopep-2 were crucial for its passage across the BBB. Overall, the results demonstrate the significant potential of this platform for the development of novel neurotherapeutics.