NSI-189
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| Routes of administration | By mouth[1] |
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| Pharmacokinetic data | |
| Elimination half-life | 17.4–20.5 hours[1] |
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| Chemical and physical data | |
| Formula | C22H30N4O |
| Molar mass | 366.509 g·mol−1 |
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NSI-189 is an experimental, potential antidepressant that was developed by Neuralstem, Inc. for the treatment for major depressive disorder (MDD), as well as for cognitive impairment and neurodegeneration.[2][1][3]
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 August 2020 another phase 2 study with 220 participants was done. A 80 mg dose of NSI-189 showed significant benefit over placebo in the subgroup of patients who were moderately depressed (MADRS < 30) but was not significant in patients who were severely depressed (MADRS ≥ 30). The study concludes that NSI-189 is effective as a safe adjunctive therapy, with most compelling antidepressant and procognitive benefits noted in patients with moderate depression.[10]
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]
In 2021, Neuralstem merged with another company to become Palisade Bio, who in 2021 sold NSI-189 to an unknown buyer for up to $4.9 million.[11]
See also
References
- ^ a b c d 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. 21 (10): 1372–80. doi:10.1038/mp.2015.178. ISSN 1359-4184. PMC 5030464. PMID 26643541.
- ^ a b c Eric E. Bouhassira (15 June 2015). The SAGE Encyclopedia of Stem Cell Research. SAGE Publications. pp. 843–. ISBN 978-1-4833-4767-7.
- ^ a b c Neuralstem (March 2016), Neuralstem Inc. March 2016 Corporate Presentation (PDF), retrieved 25 March 2016[dead link] Alt URL
- ^ "Neuralstem: NSI-189 Phase 2 Trial Fails To Meet Primary Efficacy Endpoint". NASDAQ.com. 2017-07-25. Retrieved 2017-09-20.
- ^ a b "Neuralstem Inc. Corporate Presentation" (PDF). January 2018.
- ^ Clinical trial number NCT01310881 for "Single-Dose Pharmacokinetics (PK) Study of Novel Neurogenic Compound NSI-189" at ClinicalTrials.gov
- ^ Clinical trial number NCT01520649 for "Multiple-Dose Pharmacokinetics (PK), and Pharmacodynamic (PD) Effect of NSI-189 Phosphate in Depression Patient Subjects" at ClinicalTrials.gov
- ^ "Neuralstem Announces Top-line Phase 2 Data of NSI-189 for Major Depressive Disorder". Neuralstem Inc. 25 July 2017.
- ^ Court, Emma (July 25, 2017). "UPDATE: Neuralstem stock plummets 61% on news of mid-stage clinical trial miss".
- ^ Johe, KK; Kay, G; Kumar, S; Burdick, KE; McIntyre, RS; Papakostas, GI; Fava, M (August 2020). "NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately depressed patients: A post-hoc analysis of a phase 2 study of major depressive disorder". Annals of Clinical Psychiatry. 32 (3): 182–196. PMID 32722729.
- ^ "Palisade Bio, Inc. Announces Sale of Seneca Asset NSI-189 for the treatment of Central Nervous System Disorders".