The blood-brain barrier (BBB) presents a significant obstacle to drug delivery into the brain. As such, conventional methods of medicine administration often fail to target various brain diseases. In this project, the goal is to fully focus on the development of an anti-brain cancer drug candidate. More specifically, the project aims to identify Nanobodies® that can cross the BBB or the blood-cerebrospinal-fluid barrier by receptor-mediated transcytosis in a smart in vivo screen that bypasses the current limitations of lab models.
This search for Nanobodies that can cross the BBB will the be used as a starting point for the development of novel therapeutics. Using this approach will form a new framework for the treatment of various neurological and psychiatric conditions.
The project includes an elaborated strategy for the development of our clinical candidate upon successful completion of this grant. The fact that we have generated in less than one year an effective receptor mediated transcytosis Nanobody in mice demonstrates that we are capable to deliver efficiently and effectively within the short time frame of the Grand Challenges Program.
Overall, this project has the following goals:
- Identify Nanobodies that can efficiently cross the BBB and can be used to deliver anti-brain cancer drugs.
- Develop and use a smart in vivo screen that represents a marked improvement over the limited current lab models.
- Build on the gained knowledge to begin the development of effective BBB-crossing therapeutics for brain cancer.
Facts & Figures
precision medicine will be improved by translating innovative molecular diagnostic paradigms into clinical practice
precision medicine will be improved by translating new insights in molecular mechanisms of disease into clinical practice
Contribution to the project
Bart De Strooper: "The single most important hurdle to successful therapy for brain disorders is drug delivery across the blood-brain barrier. We propose a pioneering approach to identify new, safer and more efficient treatment routes for brain disease, and a first proof-of-concept would be the delivery of treatments for breast cancer brain metastasis. Thanks to the Grand Challenges program, we can work together with the best researchers across the globe to develop game-changing solutions for the treatments of brain tumors, neurodegenerative diseases such as Alzheimer’s or Parkinson’s, or autoimmune disorders such as MS.”
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).
Core facilities involved
Both the VIB Nanobody Core and the VIB Protein Core offer newly developed methodologies to this program.
The objective of the VIB-GC program is to significantly increase the societal impact of VIB, hence taking its scientific leadership to the next level of global visibility, strategies between partners towards sharing of capabilities (samples, data, infrastructure) are prerequisite and motivated within the VIB GCP, aligned with the general principles of RRI and the Open Science policy of VIB in particular.
If the approach is successful, the strategy will be further developed to enable its use for a multitude of drugs tackling various brain conditions.
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.
“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.”