NSI-189

NSI-189 is an experimental, potential antidepressant that is under investigation by Neuralstem, Inc. for the treatment for major depressive disorder (MDD), as well as for cognitive impairment and neurodegeneration.[2][1][3]

NSI-189
Clinical data
Routes of
administration
By mouth[1]
Legal status
Legal status
Pharmacokinetic data
Elimination half-life17.4–20.5 hours[1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC22H30N4O
Molar mass366.509 g·mol−1
3D model (JSmol)

A phase II clinical trial for MDD failed to meet the primary depression endpoint (MADRS) in July 2017, although statistically significant improvements have been reported on a number of secondary depression and cognition endpoints.[4][5]

The compound's activity was discovered using phenotypic screening with a library of 10,269 compounds to identify compounds that promoted neurogenesis in vitro.[3] As of 2016 the target of the compound was unknown but it appeared to promote neurogenesis in rodents.[2][3]

NSI-189 completed a phase I clinical trial for MDD in 2011, where it was administered to 41 healthy volunteers.[6] A phase Ib clinical trial for treating MDD in 24 patients started in 2012 and completed in July 2014, with results published in December 2015.[1][7] In July 2017, it was announced that a phase II clinical trial with 220 patients failed to meet its primary effectiveness endpoint in MDD.[8] Upon the announcement, Neuralstem stock plummeted by 61%.[9] More detailed analysis of the trial results was released in December 2017 and January 2018. It revealed statistically significant improvements on patient-reported depression scales and in aspects of cognition for the 40 mg/day dose. Of particular note are improvements in memory (effect size Cohen's d = 1.12, p = 0.002), working memory (d = 0.81, p = 0.020), and executive functioning (d = 0.66, p = 0.048) as measured by the CogScreen computerized test.[5]

In addition to MDD, Neuralstem has said that it intends to pursue clinical development of NSI-189 for a variety of other neurological conditions, including traumatic brain injury, Alzheimer's disease, post-traumatic stress disorder, stroke, and to prevent cognitive and memory decline in aging.[2]

See also

References

  • McIntyre RS, Johe K, Rong C, Lee Y (2017). "The Neurogenic Compound, NSI-189 Phosphate: a Novel Multi-Domain Treatment Capable of Pro-Cognitive and Antidepressant Effects". Expert Opin Investig Drugs. 26: 767–770. doi:10.1080/13543784.2017.1324847. PMID 28460574.
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