Treatment of normal mouse brain slices with NSi-189 produced a concentration and time dependent enhancement of the magnitude of long term potentiation (LTP), a measure of synaptic plasticity, which is an in vitro biomarker of memory. Additionally, NSI-189-induced LTP enhancement requires protein synthesis, suggesting structural synaptic plasticity.

NSI-189 treatment of brain slices from mice with a genetic defect that models Angelman Syndrome (which in humans leads to inherited intellectual disability) restored LTP to normal levels.

NSI-189 treatment ameliorated behavioral and memory function and preserved hippocampal neurogenesis in a rat model of cognitive impairment induced by irradiation.

Potential Treatment for Type 1 and Type 2 Diabetes

NSI-189 was demonstrated to be effective in the prevention and reversal of peripheral neuropathies in a mouse model of Type 1 and preventative in a mouse model of Type 2 diabetes. Data from these studies, which includes reversal of neuropathic pain and decreased nerve conductance associated with the onset of diabetic symptoms, suggest that NSI-189 may have broad applicability in the treatment of central and peripheral neuropathies arising from diverse etiologies.

Potential Treatment for Ischemic Stroke

Oral administration of NSI-189 to mice with ischemic stroke led to a significant increase in neurogenesis in the hippocampus accompanied by a significant recovery from motor deficit. This evidence suggests that NSI-189 can induce recovery from stroke-induced brain damage. The improvements were maintained post the termination of NSI-189 therapy for an additional 12-week, drug-free, observational period. The sustained improvement suggests that NSI-189 initiated a host brain repair mechanism enabling tissue remodeling of the stroke brain. NSI-189 demonstrated the upregulation of growth factors such as stem cell factor (SCF) and brain-derived neurotrophic factor (BDNF), as well as increasing neurite outgrowth.