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.
|Elimination half-life||17.4–20.5 hours|
|Chemical and physical data|
|Molar mass||366.51 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.
The compound's activity was discovered using phenotypic screening with a library of 10,269 compounds to identify compounds that promoted neurogenesis in vitro. As of 2016 the target of the compound was unknown but it appeared to promote neurogenesis in rodents.
NSI-189 completed a phase I clinical trial for MDD in 2011, where it was administered to 41 healthy volunteers. 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. In July 2017, it was announced that a phase II clinical trial with 220 patients failed to meet its primary effectiveness endpoint in MDD. Upon the announcement, Neuralstem stock plummeted by 61%. 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.
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.
- 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.
- Eric E. Bouhassira (15 June 2015). The SAGE Encyclopedia of Stem Cell Research. SAGE Publications. pp. 843–. ISBN 978-1-4833-4767-7.
- Neuralstem (March 2016), Neuralstem Inc. March 2016 Corporate Presentation (PDF), archived from the original (PDF) on 31 January 2017, retrieved 25 March 2016
- "Neuralstem: NSI-189 Phase 2 Trial Fails To Meet Primary Efficacy Endpoint". NASDAQ.com. 2017-07-25. Retrieved 2017-09-20.
- "Neuralstem Inc. Corporate Presentation - January 2018" (PDF).
- "Single-Dose Pharmacokinetics (PK) Study of Novel Neurogenic Compound NSI-189 - Full Text View - ClinicalTrials.gov".
- "Multiple-Dose Pharmacokinetics (PK), and Pharmacodynamic (PD) Effect of NSI-189 Phosphate in Depression Patient Subjects - Full Text View - ClinicalTrials.gov".
- "Neuralstem Announces Top-line Phase 2 Data of NSI-189 for Major Depressive Disorder". Neuralstem Inc.
- Court, Emma (July 25, 2017). "UPDATE: Neuralstem stock plummets 61% on news of mid-stage clinical trial miss".