Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

Pedder, Josephine H, Sonabend, Adam M, Cearns, Michael D ORCID: 0000-0002-1479-8979, Michael, Benedict D ORCID: 0000-0002-8693-8926, Zakaria, Rasheed ORCID: 0000-0001-6826-2662, Heimberger, Amy B, Jenkinson, Michael D ORCID: 0000-0003-4587-2139 and Dickens, David ORCID: 0000-0001-8295-0752 (2025) Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease. The Lancet. Neurology, 24 (3). S1474-4422(24)00476-9-S1474-4422(24)00476-9. ISSN 1474-4422, 1474-4465

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Abstract

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics. These approaches each have their advantages and disadvantages. CSF delivery and intracranial delivery are direct but invasive techniques that have not yet shown efficacy in clinical trials, although development of novel delivery devices might improve these approaches. Ultrasound-based disruption has shown some efficacy in clinical trials, but it can require invasive procedures. Approaches using membrane transporters and receptor-mediated transcytosis are less invasive than are other techniques, but they can have off-target effects. Nanotherapeutics have shown promise, but these strategies are in early stages of development. Advancements in drug delivery across the blood-brain barrier will require appropriately designed and powered clinical studies, with a focus on the timing of treatment, demographic and genetic considerations, head-to-head comparison with other treatment strategies (rather than a placebo), and relevant primary and secondary outcome measures.

Item Type:	Article
Uncontrolled Keywords:	Blood-Brain Barrier, Animals, Humans, Nervous System Diseases, Drug Delivery Systems
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	04 Feb 2025 09:19
Last Modified:	27 Mar 2025 11:37
DOI:	10.1016/s1474-4422(24)00476-9
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3190091