Engineering extracellular vesicles to permeabilize the blood-brain barrier

Objetivo temático: Good Health and Well-Being

Área Científica: Ciências da saúde

Síntese do Projeto: Brain diseases, such as central nervous system (CNS) disorders and brain cancers, are some of the most prevalent, devastating and yet poorly treated diseases. According to a recent study led by Roche [1], in 2020, the total cost of neurological disorders in Europe was $1.06 tn, equivalent to the cost of heart diseases, cancer and diabetes combined. The global drug development for brain diseases has to grow rapidly in the next years to address this global challenge. Unfortunately, drug development for brain diseases has the poorest success rates compared to other therapeutic areas. This is largely due to our difficulty to deliver drugs in the brain as a consequence of the low permeability of the blood brain barrier (BBB). The BBB is a physical and metabolic barrier that prevents undesired substances from reaching the brain. It is formed by endothelial cells (ECs) that interact with the other cells of the neurovascular unit, such as pericytes, astrocytes, and neurons. This interaction contributes for the maintenance of the main brain ECs (BECs) features such as a low pinocytotic activity, reduced transcytosis, a higher density of mitochondria, and tight junctions (TJs) proteins, contributing to a low permeability. In recent years, several strategies have been investigated to open transiently the BBB to facilitate the delivery of drugs to the brain; however, with limited efficacy. The BBB permeability increases during aging and this can be an inspiration for the development of strategies to overcome the biological barrier. It is likely, that part of this regulatory effect of the blood in the BBB might be mediated by small extracellular vesicles (sEVs). sEVs are biological nanoparticles delimited by a lipid bilayer and containing several types of biomolecules, including noncoding RNAs. The goal of this project is to investigate whether sEVs enriched with miRNAs over-expressed during aging can transiently open the BBB.

Investigador Responsável na UC: Aji Alex Moothedathu Raynold

Unidade Orgânica UC: Universidade de Coimbra

Instituições participantes no projeto: Universidade de Coimbra (UC)

Instituição Financiadora/Gestora: FCT-Fundação p/a Ciência e a Tecnologia

Programa de Financiamento: Projetos Exploratórios em Todos os Domínios Científicos 2023

Período de execução: 01/01/2025 a 30/06/2026

Custo total elegível (EUR): 49963,43

Apoio financeiro público nacional: 49963,43

Técnico do projeto: Sónia Branco

Contacto: +351 239 247 019 | sonia.branco@uc.pt