Novel Antidepressant Shows Promise in Phase 1
NSI-189 has demonstrated the ability to produce new brain cells and has been effective in early stage trials.
A novel drug under early clinical development that has demonstrated the ability to produce new brain cells is being eyed as a potential depression treatment.
Maurizio Fava, MD, executive director of the Clinical Trials Network & Institute (CTNI) in the Massachusetts General Hospital Department of Psychiatry, Boston, and colleagues, have are examining the potential of NSI-189, which was developed by Neuralstem. Animal studies have been conducted by the company.
A phase 1a trial in healthy subjects was conducted in 2011. In the latest trial, a phase IIb designed to determine the safety and maximum dose of NSI-189 that could be safely administered, 24 adult patients with major depressive disorder were enrolled.
They were randomized into one of three groups. In each group of eight subjects, six received NSI-189 and two received placebo. Those who were taking the active drug received a 40 mg dose either once, twice or three times daily. After 28 days of treatment, participants were followed for another 56 days.
On four measures of depressive or cognitive symptoms, participants receiving the active drugs showed improvement after the 28-day treatment period, with significant differences from the placebo group on two measures based on participants' self-reports, the researchers reported in the journal Molecular Psychiatry. Adverse events reports were similar in both those on placebo and the active drug, even in those taking the highest dose.
EEG readings taken before and during treatment an increase in high-frequency alpha waves, and MRI scans suggested the possibility of increased hippocampal volume in those taking NSI-189.
A larger phase II study has been designed and initiated.
Fava M, et al. A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol Psychiatry. 2015; doi: 10.1038/mp.2015.178.