Developing Topics.

Background: Adult Hippocampal Neurogenesis has been shown to be involved in Major Depressive Disorder (MDD) and Alzheimer's disease (AD) pathology. NA-831 is a small drug molecule, exhibiting neuroprotection, neurogenesis and memory enhancing properties.

Method: For AD: A randomized clinical trial of NA-831 was performed in 112 participants with mild and moderate Alzheimer's disease (AD), half received the drugs and half received placebo. The patients with MCI received 10 mg of NA-831 and patients with mild and moderate AD received 30 mg of NA-831 or placebo orally per day. Subjects with MCI met the NIA-AA core criteria. CDR score of 0.5 and a Memory Box score of 0.5 or greater at Screening and Baseline. MMSE score ≥22. Subjects with mild & moderate AD to meet the NIA-AA core criteria. MMSE: 17-21. For MDD: A randomized, clinical study was conducted to investigate the efficacy and safety of two fixed doses (20 and 40 mg/d) of NA-831 vs. that of placebo after 6-week treatment in 32 adult patients with major depressive disorder (MDD).

Result: For AD: NA-831 showed a significant improvement for patients with mild and moderate AD with the ADAS-Cog-13 score change of an average of 4.1 as compared to the placebo after 24 weeks of treatment (p = 0.001; ITT). CIBIC-Plus showed 78% patients improved (p = 0.01; ITT). mNA-831 was well-tolerated at 30 mg/day. There were no serious adverse events observed. For MDD: The difference between active treatment and placebo of ∼7 points on the MADRS translates into a clinically relevant difference in response rates of 32.5% units, compared to an average of 16% units for antidepressants approved by the USA FDA. Treatment with NA-831 for 6-week was well tolerated and efficacious in reducing depressive and anxious symptoms in patients with MDD.

Conclusion: The Neurogenesis Hypothesis has been shown to be a viable approach for further research for Alzheimer's disease and Major Depressive Disorder. Phase 3 trials of NA-831 for the treatment of AD and MDD are being conducted. Results of the clinical trials will be provided as soon as they are available.