Non-invasive Bdnf mRNA therapy improves cognition in ageing and Alzheimers mouse models

Authors

Bergamasco, M. I., Clark, T., Loo, L., Fujikake, K., Carr, R., Scarborough, H., Ponta, A., Holsinger, R. M. D., Neely, G. G.

Abstract

Messenger RNA (mRNA) therapeutics have rapidly emerged as a transformative approach for treating a range of health challenges. Accelerated by the success of mRNA-lipid nanoparticle (LNP) vaccines during the COVID-19 pandemic, this platform holds promise beyond immunisation for the transient expression of therapeutic proteins in targeted tissues. Despite this promise, non-invasive delivery of mRNA to the brain, as with most therapeutics, remains a challenge due to the impermeability of the blood brain barrier. Here, we present a novel strategy to deliver neurotrophic factors to the brain via intranasal delivery of mRNA-LNP. As a proof of concept, we demonstrate that intranasal delivery of mRNA encoding the neurogenic factor BDNF (Brain Derived Neurotrophic Factor) enhances memory performance in both aged mice and a transgenic mouse model of Alzheimers disease. This approach offers a promising platform for delivering therapeutic proteins to the brain and opens new avenues for treating age-related and neurodegenerative disorders.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 21 Apr 2026.

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