GT 1061 is a novel therapeutic agent that is in Phase 1 clinical studies for
Alzheimer's disease.
GT 1061 is one of a family of novel
nitrates that have demonstrated neuroprotective properties and cognition- and memory-enhancing properties in animal models. The prototype of this family,
GT 715, has been reported effectively to dissociate the neuromodulatory and the systemic hypotensive effects of
nitrates, the latter seriously limiting the
therapeutic use of classical
nitrates. Further data on the novel
nitrates,
GT 715 and
GT 061, are presented in (a) the
malonate-lesion rat model of excitotoxic neurodegeneration, and (b) the reversal of a
scopolamine-induced cognition deficit in the Morris water task which tests spatial memory. These data exemplify and reinforce the combined neuroprotective and cognition enhancing properties observed in this family of NO mimetic therapeutic agents. NO mimetics, that mimic the
biological activity of NO, will bypass
cholinergic receptor activation and are anticipated to provide multiple pathways of treating and circumventing
dementia. NO mimetic activation of
soluble guanylyl cyclase and cGMP formation in the brain represents one
element of an effective neuroprotective strategy. Substantial evidence suggests that NO mimetics may display cGMP-dependent and cGMP-independent activity and may operate via multiple biochemical signaling pathways, both to ensure the survival of neurons subjected to stress and also to provide cognition-enabling pathways to circumvent
dementia, providing a combined neuroprotective and cognition-enabling approach to anti-neurodegenerative
therapy.