COVID-19 is primarily a respiratory disease; however, neurological symptoms are also reported in a subpopulation of infected COVID-19 individuals. Complementary studies combining neuroimaging and cognitive screening implicate COVID-19-induced impairment of the frontal cortex, a critical area for cognitive function. Our researchers discovered that brain gene profiles of severe COVID-19 patients have increased expression of innate immune response genes and genes implicated in AD pathogenesis. Specifically, they identified AD brain signatures involved in inflammation, protein folding/trafficking, amyloid processing, and tau phosphorylation/ oligomerization.
This invention provides a method of preventing AD onset following severe COVID using a novel RNA-nanosystem carrying dual (brain and CNS)-targeted dendriplexes (DPX) delivered via the nose-to-brain axis. The RNA-nanosystem is based on RNAi targeting the increased expression of FKBP51, NLRP3, or IFI16 in patients. This aims to regulate inflammatory cytokines and mediators, reducing inflammation-induced neurodegeneration. These DPXs provide the opportunity to combine the payloads producing short hairpin RNAs (shRNAs) targeting neuro-inflammation and/or neurodegeneration.
Experiments conducted using mice of different ages (3, 6, and 20 months) and infected with the SARS-CoV-2 MA10 virus. After 18 days of infection, the mouse brains were examined using a staining technique to detect a protein called a-synuclein. The results showed increased levels of a-synuclein in specific brain regions, such as the olfactory bulb, cortex, and hippocampus, in the infected mice compared to uninfected mice. This suggests that SARS-CoV-2 infection may lead to higher expression of a-synuclein in the brains of older mice.