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.
Show 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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