Beyond the BBB · Nerve Growth Factor Delivery into the Brain – focus on therapeutic potential in Alzheimer’s disease and In Vivo Evaluation via PET

Nerve Growth Factor Delivery into the Brain – focus on therapeutic potential in Alzheimer’s disease and In Vivo Evaluation via PET

Diseases of the brain, including Alzheimer’s disease and other neurodegenerative disorders, remain some of the most difficult to treat. One of the major obstacles is the blood-brain barrier (BBB)—a natural defence system that protects the brain but also blocks the entry of most drugs into the brain. While biologics (such as antibodies and neurotrophic factors) hold great promise for brain therapy, delivering them effectively and monitoring their impact remains a significant challenge in neuroscience and drug development. This project addressed this issue by developing a non-invasive strategy to deliver biologics into the brain and visualising their engagement with disease-relevant targets using PET imaging (Positron Emission Tomography). The original approach involved modifying nerve growth factor (NGF) for brain delivery, targeting its receptor (TrkA), and assessing successful targeting binding using a newly designed PET tracer. However, due to technical challenges with NGF production, the project pivoted to a more flexible and robust strategy: developing a pretargeted PET imaging platform based on bioorthogonal click chemistry (specifically, TCO–tetrazine ligation). This approach decouples the therapeutic molecule from the radiotracer, offering a safer, more modular way to monitor drug delivery to the brain in real time. To support this strategy, the project also implemented a focused ultrasound (FUS) technique that allows temporary opening of the BBB in animal models. This combination of technologies was designed to significantly improve the precision of brain-targeted delivery and the ability to measure whether therapeutic agents reach their intended targets. This research solves a bottleneck in brain drug development: the lack of practical tools to assess whether large biologics reach the brain and bind to their intended targets. The imaging method developed during this fellowship offers the potential to: - Accelerate the development of brain-targeted drugs by providing quantitative imaging of drug-target engagement - Improve diagnostic and therapeutic precision for neurodegenerative diseases. While the original scientific approach was revised, the project maintained its overall objectives and adapted to technical challenges, yielding promising results.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз