Scientists from the University of Liverpool, and their global collaborators have highlighted the most effective treatments for neurological diseases by overcoming one of medicine's most difficult challenges: the blood-brain barrier. Led by Dr David Dickens, their findings offer new hope for patients with conditions including Alzheimer's, and Parkinson's disease, brain tumours, and epilepsy.
The blood-brain barrier acts as a highly selective shield that protects the brain from harmful substances in the bloodstream. However, this same protective feature makes it difficult for most medications to reach the brain. Researchers estimate that this barrier blocks more than 98% of small-molecule drugs and nearly 100% of larger therapeutic agents, severely limiting treatment options for brain-related illnesses.
Now, a new study published in the Lancet Neurology highlights several pioneering strategies that show promise for safely bypassing this barrier. The team analysed existing studies within the last five years that investigate a range of treatments. By pooling the knowledge generated in each of these studies, new insights have been discovered, revealing the most effective methods of treatment to cross the blood-brain barrier. They include:
• Ultrasound Technology: Focused ultrasound waves, combined with tiny bubbles injected into the bloodstream, temporarily open the blood-brain barrier, allowing medications to reach the brain. This method has shown potential in enhancing drug delivery for Alzheimer's disease and certain brain cancers.
• Nanotechnology: Tiny nanoparticles are being used to deliver drugs directly to brain cells. These particles can carry therapeutic agents across the blood-brain barrier while minimizing side effects.
• Targeted Drug Delivery: Innovative techniques using naturally occurring transport systems in the body are being developed to guide drugs across the barrier, specifically targeting affected areas in the brain.
• Direct Brain Injections: For conditions like Parkinson's disease or brain tumours, advanced delivery devices allow precise injections of medication or therapeutic viruses directly into the brain.
Dr David Dickens, Lecturer in the Department of Pharmacology & Therapeutics at the University of Liverpool said: "The blood-brain barrier has long been a bottleneck in treating neurological diseases. These cutting-edge approaches are enabling us to bring treatments directly to the brain, improving efficacy and reducing risks. My lab has extensive expertise in targeted drug delivery to the brain and has established a cutting-edge cellular blood-brain barrier model for drug and disease modelling. This means we are at the forefront of research into this exciting area of unmet need."
Early clinical trials have already demonstrated encouraging results. For example, focused ultrasound has successfully increased drug penetration in patients with brain metastases and glioblastoma. Similarly, targeted drug delivery has shown promise in targeting aggressive brain tumours.
However, researchers caution that many of these methods are still in their infancy and require further validation in clinical trials, understanding of transport processes and utilisation of advanced cellular models of the blood-brain barrier. Dr Dickens continues: "While we are seeing exciting progress there remains a need for continued investment in research to refine these techniques and expand their application to other neurological conditions. However, these breakthroughs could transform the way we treat brain diseases, offering new hope to millions of patients worldwide."
The review, 'Crossing the Blood-Brain Barrier: Emerging Therapeutic Strategies for Neurological Disease' was published in Lancet Neurology. (DOI:10.1016/S1474-4422(24)00476-9).
