[Researcher of the Month] Finding a Cure Through Direct Intranasal Delivery
Lee Sang-kyung (Department of Bioengineering)
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Flaviviruses like the West Nile virus (WNV), Japanese encephalitis (JEV), and Zika are neurotropic, causing neurological complications or death to those with low immune systems. There is now a cure in development called the siRNA approach which has demonstrated promising results in treating viral infections in animal models. However, several complications exist when it comes to treating humans. Lee Sang-kyung (Department of Bioengineering), along with his fellow researchers, has come up with a solution in his paper "Small Interfering RNA-Mediated Control of Virus Replication in the CNS is Therapeutic and Enables Natural Immunity to West Nile Virus."
The small interfering RNA (siRNA) is a therapeutic strategy targeting illnesses such as cancer, inflammation, and genetic disorders. This strategy was proven to be successful in treating various viral infections including encephalitis-induced morbidity and mortality, in animal subjects. However, there have been several complications regarding its application to human brains.
One of the challenges was due to human anatomy being quite different from that of animal test subjects like mice. After the long research process, it was clear that direct delivery of siRNA to the brain was the best method of treatment. However, not only was finding the right treatment of viral encephalitis (inflammation of the brain) challenging, but the direct delivery of siRNA effectively across the blood-brain barrier (BBB) was a huge block as well. The blood-brain barrier is a filtering mechanism of the capillaries that carries blood to the brain and spinal cord tissue, blocking the passage of certain substances. This basically means that intruding substances are blocked so nothing goes in, and nothing goes out. This makes it harder for the research to continue.
To overcome this problem, Lee and his fellow researchers came up with the intranasal delivery method that allows a substance's direct delivery to the brain while circumventing the challenges associated with the blood-brain barrier. This method was based on the unique connection in human anatomy between the brain and the outer world through the olfactory nerve. Lee was able to invent an intranasal delivery device for WNV-infected mice at late stages of the neuroinvasive disease in hopes of demonstrating that the treatment would bring results in recovery. The mice seated on the platform were naturally placed into the "Mecca" position, which is the best angle for proper direct drug delivery.
The siRNA delivered through this route revealed a remarkable therapeutic effect in reducing brain viral load, neuropathology, and mortality even when the treatment was initiated at late stages of WNV infection. Furthermore, the treatment allowed the natural protective immune responses to be triggered outside of the brain that would result in prevention after recovery. This discovery will allow active studies to be conducted in brain research and therapy in the future.
However, there are still more challenges to overcome. Animal subjects used in the experiments such as mice, have the anatomical difference of having a nasal cavity that is six times larger than that of a human being's. This means that the amount of the substance that can be absorbed through a human nasal epithelium (a type of animal tissue) is reduced. The "Mecca" position is a crucial discovery in the steps to overcoming such challenge, but further research is needed. Lee hopes that through the use of the intranasal drug delivery device, they will be able to discover the optimized method of delivery which will be suitable to human anatomy, thus preventing thousands from suffering and death.
Lee's research and discovery can be read in detail in the Cell Host & Microbe scientific journal as well as on Signet Biotech's website (signetbiotech.com).
Park Joo-hyun firstname.lastname@example.org
Photos by Lee Jin-myung
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