According to the World Health Organization (WHO), neurological disorders, ranging from epilepsy to Alzheimer’s disease, affect up to one billion people worldwide. These neurological disorders affect people in all countries, irrespective of age, sex, education, or income. The impact of these conditions on healthcare systems across the globe is enormous, and with an aging population in many countries this burden is likely to increase. Patients do not only experience difficulties in the practicalities of life, but also in their emotional and psychological experiences.

It is clear that the quest for new and improved medication should proceed unabated. There is, however, a major challenge affecting potential treatment for all brain disorders: the blood-brainbarrier (BBB). This barrier protects the brain from external threats while allowing nutrients to pass through. Unfortunately, very few drugs can easily cross the BBB, which renders many potentially promising treatment options practically useless. This Grand Challenges project will explore an advanced approach to ferry drugs across the BBB and transport them to the sites where they are needed to have maximum impact.​


The project aims to identify Nanobodies® that can cross the BBB or the blood-cerebrospinal-fluid barrier by receptor-mediated transport (RMT) in a smart in vivo screen that bypasses the current limitations of lab models. Main milestones in the project will be:

- the development of a Nanobody®-based strategy that enables drugs to cross the BBB

- testing this strategy in late-stage preclinical models representing breast cancer patients with metastases

in the brain that are unamenable to surgery or other forms of treatment

If the approach is successful, the strategy will be further developed to enable its use for a multitude of drugs tackling various brain conditions.​

​Frederik De Smet (KU Leuven) emphasizes the translational aspect of the project: “Once we get the transport mechanism working, we want to bring this to clinical practice quickly and develop it into applications that benefit patients, for example people suffering from metastasized tumors in the brain.”



​The multidisciplinary consortium includes Bart De Strooper (VIB-KU Leuven Center for Brain & Disease Research), Maarten Dewilde (VIB Discovery Sciences), Roosmarijn Vandenbroucke (VIB-UGent Inflammation Research Center).

Also involved are Peter Janssen (KU Leuven), Frederik De Smet (KU Leuven), Paul Declerck & Nick Geukens (PharmAbs, KU Leuven), Sebastian Haesler (Neuro- Electronics Research Flanders, VIB- KU Leuven-Imec) and Benedikt Kessler (University of Oxford, UK). The project in addition is supported by Johannes Van Loon & Tom Theys (University Hospitals Leuven-KU Leuven) and Thomas Birngruber (Joanneum Research, Austria).​


Societal impact

This project will greatly increase our current understanding of the challenges in drug delivery to the brain and their impact on the treatment of neurological disorders. If successful, this opens a completely new field of options to treat neurological and neurodegenerative disorders. Such a high-risk but high-gain milestone technology platform can enable large-scale societal alleviation of brain disease burden on both the individual patient level and healthcare systems.​


Go back to the overview: 'the Grand Challenges Program'​