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New drug for brain disease: mRNA




Researchers at Tokyo Medical and Dental University (TMDU) are demonstrating an mRNA delivery system that effectively produces BDNF protein in the rat brain to protect neurons from ischemia.

Tokyo-A lack of oxygen in the brain tissue known as ischemia leads to the death of the neurons that cause the stroke. Despite considerable research, there is currently no cure to successfully prevent neuronal cell death. Researchers at Tokyo Medical and Dental University (TMDU) are currently reporting how to deliver mRNA to produce therapeutic proteins that protect neurons. Their findings demonstrated in rats are published in Biomaterials.

Brain-derived neurotrophic factor (BDNF) is a protein that enhances the survival and function of neurons. However, BDNF is difficult to establish its therapeutic status because BDNF molecules are too large to cross the protective barrier of the brain and are rapidly removed from the central nervous system.

Therefore, researchers have devised a way to generate BDNF where it is most needed.

They designed a delivery system that contains BDNF messenger RNA (mRNA), the information molecule needed to make BDNF. Once the mRNA enters the cell, it can be used as a blueprint for making proteins.

Their system (known as mRNA nanomicelles) is a parcel of mRNA that resembles a small ball surrounded by polymer chains. Polymers help protect mRNA from molecules that can break it down and hide it from the immune system.

“In addition to protecting mRNA by providing containment, polymers allow us to control cargo release,” explains Yuta Fukushima, lead author of the study. “Choosing a polymer with specific properties ensures that mRNA is released when and where it is needed.”

The efficacy of mRNA therapy was tested in rats that experienced cerebral ischemia. Nanomicelles have been found to increase the survival of hippocampal neurons. In particular, nanomicelles showed better effects when administered 2 days after ischemia than when administered immediately. This shows that nanomicelles are expanding the opportunities to provide effective treatments.

In addition, long-term therapeutic effects were observed 20 days after ischemia when mRNA nanomicelles were administered on both days 2 and 5. In maze experiments, treated rats showed better spatial memory than untreated rats.

“We are very encouraged by the performance of our system,” said Keiji Itataka, the author of the study. “Our experiments have also shown that mRNA nanomicelles can not only prevent neuronal death, but also expand the potential treatment window. These findings will have a significant impact on the development of actual clinical therapies. I’m expecting it. “

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