Targeting neuroinflammatory pathways using Nanoligomers™ is neuroprotective in prion disease

Abstract

AbstractNeuroinflammation is a key factor in the development of neurodegenerative diseases, including prion disease. There are currently no effective treatments to halt pathogenesis and progression, which includes accumulation of misfolded proteins, neuroinflammation, and cognitive/behavioral deficits followed by irreversible neuronal death. We hypothesized that downregulation of two key neuroinflammatory targets would be neuroprotective. To test this, we utilized Nanoligomers™ in a prion-diseased mouse to assess the impact on glial inflammation, behavioral/cognition deficits, and loss of neurons. Nanoligomer™ treated mice displayed decreased numbers of glia, and improved behavior and cognitive tests. Critically, the Nanoligomer™ protected the brain from prion-induced spongiotic change, neuronal loss, and significantly increased life span, indicating that Nanoligomer™ inhibition of inflammatory pathways can prevent neuronal death and slow the progression of neurodegenerative diseases.One-Sentence SummaryImmunotherapeutic Nanoligomer™ in prion diseased mice opens new treatment avenues for other neurodegenerative diseases.