mRNA Delivery System Protects Neurons After Stroke

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Researchers at the Tokyo Medical and Dental University have developed a way to deliver therapeutic mRNA to the brain, in this case to produce brain-derived neurotrophic factor (BDNF) which can protect neurons from ischemia. The researchers hope that the treatment could help patients who have suffered a stroke to achieve better outcomes by reducing cell death.

mRNA is enjoying a moment in the spotlight, with two of the most effective COVID-19 vaccines using it to produce an immune response against the virus. However, mRNA has significant therapeutic potential beyond vaccination, and this latest research investigates its potential to protect neurons in the brain from ischemia following a stroke.

This treatment is based on BDNF, a protein that can protect neurons and enhance their survival. In a stroke, neurons in the brain experience ischemia, but BDNF is too large to pass through the blood-brain barrier.

These researchers came up with a cunning plan – rather than try to deliver the BDNF protein directly, they set out to deliver mRNA that codes for BDNF, which would be translated into the mature protein in the brain.

While the mRNA is small enough to pass through the blood brain barrier, it is too delicate to just be injected straight into the blood stream unprotected. The solution turned out to be mRNA nanomicelles, consisting of a small amount of mRNA surrounded by a polymer package to protect it in the blood and allow it to pass into the brain intact.

“As well as protecting the mRNA by providing containment, the polymer allows the release of the cargo to be controlled,” said Yuta Fukushima, a researcher involved in the study. “By selecting polymers with particular properties, we can ensure the mRNA is released when and where it is needed.”

So far, the researchers have tested their treatment in rats with cerebral ischemia. They found that the mRNA therapy increased hippocampal neuron survival and increased rat performance in a maze task. Interestingly, the treatment worked best when it was administered two days after the “stroke” rather than right away, suggesting that it might provide an extended window for effective therapy.

“We are very encouraged by the performance of our system,” said Keiji Itaka, another researcher involved in the study. “Our experiments not only demonstrated that the mRNA nanomicelles 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.”

Study in journal Biomaterials: Treatment of ischemic neuronal death by introducing brain-derived neurotrophic factor mRNA using polyplex nanomicelle

Via: Tokyo Medical and Dental University





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