Brain Endothelium - TARgeted Gene therapy to improve Aβ clearance in Alzheimer’s Disease

Alzheimer disease (AD) is the most common cause of dementia (60-80% of cases) with a prevalence near 50 million people.

There is no cure available and there are only two classes of approved drugs that are effective in treat some of the cognitive symptoms and potentially delay the clinical decline.

Despite the considerable progress achieved in the research of best performing disease-modifying agents, the main clinical challenge remains the accomplishment of an efficient and safe therapeutic option that can arrest the disease progression and prevent cognitive failure.

In this project, I am proposing an innovative approach to improve AD pathophysiology by targeting the brain endothelium to improve the Amyloid-β (Aβ) clearance using gene therapy. I will use super-selective nanocarriers to carry relevant genes for the enhancement of the Aβ clearance mechanism.

These nanocarriers will be functionalised to allow the specific targeting of brain endothelial cells and to increase its potency to deliver the therapeutic gene into these cells.

This project will combine for the first time, the use of super-selective binding strategies and gene therapy for brain endothelium targeting and modulation in the context of AD.

Overall, I will develop an innovative therapy for AD treatment, capable of reaching the BBB in a non-invasive way, being able to target the brain endothelium, overcome the defective Aβ transendothelial clearance, and potentially arrest the disease progression and prevent cognitive failure.

Therefore, this project will reach a global impact by substantially contributing with a novel avenue to change the clinical course of AD pathogenesis.