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
Pregnancy
category
  • US: N (Not classified yet)
    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
    1. Fava, M; Johe, K; Ereshefsky, L; Gertsik, L G; English, B A; Bilello, J A; Thurmond, L M; Johnstone, J; Dickerson, B C; Makris, N; Hoeppner, B B; Flynn, M; Mischoulon, D; Kinrys, G; Freeman, M P (2015). "A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients". Molecular Psychiatry. doi:10.1038/mp.2015.178. ISSN 1359-4184. PMC 5030463.
    2. Eric E. Bouhassira (15 June 2015). The SAGE Encyclopedia of Stem Cell Research. SAGE Publications. pp. 843–. ISBN 978-1-4833-4767-7.
    3. Neuralstem (March 2016), Neuralstem Inc. March 2016 Corporate Presentation (PDF), archived from the original (PDF) on 31 January 2017, retrieved 25 March 2016
    4. "Neuralstem: NSI-189 Phase 2 Trial Fails To Meet Primary Efficacy Endpoint". NASDAQ.com. 2017-07-25. Retrieved 2017-09-20.
    5. "Neuralstem Inc. Corporate Presentation - January 2018" (PDF).
    6. "Single-Dose Pharmacokinetics (PK) Study of Novel Neurogenic Compound NSI-189 - Full Text View - ClinicalTrials.gov".
    7. "Multiple-Dose Pharmacokinetics (PK), and Pharmacodynamic (PD) Effect of NSI-189 Phosphate in Depression Patient Subjects - Full Text View - ClinicalTrials.gov".
    8. "Neuralstem Announces Top-line Phase 2 Data of NSI-189 for Major Depressive Disorder". Neuralstem Inc.
    9. Court, Emma (July 25, 2017). "UPDATE: Neuralstem stock plummets 61% on news of mid-stage clinical trial miss".
    • 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. doi:10.1080/13543784.2017.1324847. PMID 28460574.


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