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bioRxiv · 10.64898/2026.04.19.719519

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

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

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Bergamasco, M. I., Clark, T., Loo, L., Fujikake, K., Carr, R., Scarborough, H., Ponta, A., Holsinger, R. M. D., Neely, G. G.. 2026-04-20. Non-invasive Bdnf mRNA therapy improves cognition in ageing and Alzheimers mouse models. https://doi.org/10.64898/2026.04.19.719519

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