Cycle 1 project 7

Molecular Imaging of Blood Brain Barrier Alterations with new peptide ligands


PhD student: Jeinny Karina Vargas Sanchez, Colombia
Home Institute: Bordeaux Neurocampus; Principle Investigator: Klaus Petry
Host Institute: Amsterdam Neuroscience; Principle Investigator: Elga de Vries

Executive Summary
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that leads to severe neurological deficits. Pathologically, MS is characterized by demyelination and axonal damage, induced by infiltrated leukocytes. Importantly, the invasion of the central nervous system (CNS) by leukocytes depends on complex molecular alterations of microvascular endothelial cells at the blood brain barrier (BBB) that are still poorly understood. These molecular alterations provide the opportunity to target specifically the areas undergoing acute inflammatory lesion formation, although to date the spatiotemporal changes at the BBB during MS remain unknown.

To visualize the events at the BBB that underlie MS lesion formation in time, selective imaging tools to distinguish and understand the molecular alteration are highly sought after. In order to develop such selective markers, we have applied phage displayed heptapeptides screening and have already isolated potential candidates that bind to molecules expressed in various cells interacting with inflamed BBB.

The overall aim of this project is now to identify peptide ligands that bind to 2 specifically or highly expressed targets at the BBB during early / acute neuroinflammation in the experimental allergic encephalomyelitis (EAE) rat model. Next, their use as selective imaging tool will be validated in vivo using magnetic resonance imaging (MRI). Importantly, through this joined grant proposal, we will be able to translate our findings to the human situation by validating their expression at various stages of well-characterized human MS lesions. This project will in future lead to novel imaging tools to detect pathological events ongoing in MS patients and opens the avenue for selective drug targeting to the brain at various pathological conditions.

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