Evaluating Soluble Guanylate Cyclase Stimulation for Serious Central Nervous System Diseases

9th International Conference on cGMP (2019)

Christopher Winrow, Juli Jones, Rajesh Iyengar, Susana Correia, Sarah Jacobson, Guang Liu, Peter Germano, Jose Trevejo, John Hadcock, Todd Milne, Mark Currie

This presentation provides an overview of a series of nonclinical studies evaluating the effects of the CNS-penetrant sGC stimulator, IW-6463. In these studies, IW-6463 suppressed markers of neuroinflammation; enhanced blood flow in brain regions associated with cognition, as monitored by fMRI-BOLD; and increased gamma wave activity in the brains of rodents. In chronic rodent studies with IW-6463, improvements in dendritic spine density/structure and restoration of cognitive performance were observed.

In quantitative EEG studies, the CNS-penetrant sGC stimulator IW-6463 elicited an increase in gamma band intensity, which has been associated with cognitive processing, while a peripheral sGC stimulator did not

Male rats were administered IW-6463 or a peripheral sGC stimulator during normal active phase with quantitative electroencephalography (qEEG) monitoring of cortical brain activity Winrow et al. (cGMP 2019) oral presentation

Exploring a powerful pathway to develop a potential treatment for neurodegenerative diseases

The nitric oxide-sGC-cGMP signaling pathway plays a fundamental role in regulating diverse physiological processes within the central nervous system, including blood flow, inflammation, neuroprotection, neuronal signaling, and metabolism. An sGC stimulator that targets the central nervous system may therefore provide therapeutic benefits in neurodegenerative diseases. Chris Winrow, Cyclerion’s IW-6463 program leader, discusses a series of nonclinical studies evaluating IW-6463.

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