A new agent for brain diseases: mRNA
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A new agent for brain diseases: mRNA

A new agent for brain diseases: mRNA

Brain-derived neurotrophic factor mRNA therapeutics for ischemic neuronal death using polyplex nanomicelle. Department of Biofunction Research,TMDU©

Brain-derived neurotrophic factor (BDNF) enhances the survival and function of neurons and could serve as a potential candidate neuroprotective agent. However, this protein is too large to cross the brain’s protective barrier and is rapidly removed from the central nervous system, making it difficult for BDNF to make its mark as a treatment. Researchers from Tokyo Medical and Dental University (TMDU) have reported a way of delivering mRNA to produce BDNF in rat brain to protect neurons from ischemia. Their findings are now published in Biomaterials.

Fukushima et al designed a delivery system containing BDNF mRNA encapsulated in a nanomicelle  to protect the mRNA from  degradation.  This polyplex nanomicelle was extensively introduced into the astrocytes to generate a higher level BDNF protein in ischemic lesion.  « As well as protecting the mRNA by providing containment, the polymer allows the release of the cargo to be controlled,  study first author Yuta Fukushima explains. By selecting polymers with particular properties, we can ensure the mRNA is released when and where it is needed.» The effectiveness of the mRNA therapy was tested on rats that had experienced brain ischemia. The nanomicelles were found to increase the survival of hippocampal neurons. In particular, the nanomicelles showed better effects when administered 2 days after the ischemia than when given immediately. This indicates that the nanomicelles extend the opportunity for providing effective treatment. In addition, long-term therapeutic benefits were observed 20 days after ischemia when the mRNA nanomicelle was administered on both days 2 and 5. Treated rats showed better spatial memory than untreated rats in a maze experiment. «We are very encouraged by the performance of our system, says study corresponding author Keiji Itaka. Our experiments not only demonstrated that the mRNA nanomicelle could prevent neuron death, but also that the potential treatment window could be extended. We expect these findings to have a significant impact on the development of practical clinical treatments.»

Anne-Lise Berthier (08-04-2021)