NSI-189 is a chemical compound developed by Neuralstem, Inc., currently under scientific investigation for its potential effects on the brain. It remains a research compound and is not an approved treatment for any condition.
Understanding NSI-189
NSI-189 is classified as an experimental neurogenic compound, studied for its ability to stimulate new brain cell growth. It originated from Neuralstem, Inc., a biopharmaceutical company focused on developing treatments for central nervous system conditions. As a small molecule, it can cross the blood-brain barrier to exert its effects within the brain. NSI-189 has been referred to as ALTO-100 in recent developments.
Investigated Mechanisms
NSI-189’s actions are hypothesized to influence brain structure and function. It is thought to promote neurogenesis, the generation of new neurons, particularly in the hippocampus, a brain region associated with mood and memory. NSI-189 may also enhance synaptic plasticity, the ability of neuronal connections to strengthen or weaken, potentially improving brain communication. This compound is believed to upregulate neurogenic factors like brain-derived neurotrophic factor (BDNF) and stem cell factor (SCF), proteins supporting neuronal survival, growth, and differentiation. While exact molecular targets are not fully elucidated, NSI-189’s mechanism appears distinct from conventional antidepressants that primarily target monoamine neurotransmitters.
Potential Therapeutic Applications
NSI-189 has primarily been investigated for its potential in treating major depressive disorder (MDD). Researchers have also explored its utility in other neurological and psychiatric conditions, including:
Cognitive impairment
Post-traumatic stress disorder (PTSD)
Traumatic brain injury (TBI)
Alzheimer’s disease
Angelman syndrome
Stroke
Age-related cognitive decline
It is important to emphasize that these are areas of ongoing investigation and do not represent established therapeutic applications.
Research Progress and Findings
NSI-189 has progressed through various phases of clinical trials, including Phase 1 and Phase 2 studies. A Phase 1b trial in 24 patients with MDD showed promising results, with participants experiencing improvements in depression and cognitive symptoms that persisted eight weeks after treatment cessation. However, a larger Phase 2 study involving 220 patients with MDD did not meet its primary endpoint of significantly improving Montgomery-Åsberg Depression Rating Scale (MADRS) scores compared to placebo for either the 40 mg or 80 mg daily doses.
Despite this, the 40 mg dose showed statistically significant improvements on secondary patient-rated measures like the Symptoms of Depression Questionnaire (SDQ) and Cognitive and Physical Functioning Questionnaire (CPFQ). Further analysis of the Phase 2 data suggested that NSI-189 provided more compelling antidepressant and pro-cognitive benefits in patients with moderate depression compared to those with severe depression. In 2021, Neuralstem sold NSI-189, now developed by Alto Neuroscience under the name ALTO-100, with new Phase 2 trials demonstrating preliminary effectiveness in MDD, particularly in patients with a specific cognitive biomarker.
Safety Profile and Regulatory Standing
Clinical trials have indicated that NSI-189 is generally well tolerated. In a Phase 1b study, no serious adverse events were reported across various doses. The compound’s half-life in the body is approximately 17.4 to 20.5 hours, and steady-state concentrations are typically reached within 96 to 120 hours. However, the full long-term safety profile of NSI-189 is not yet established due to its experimental nature.
In the United States, NSI-189 holds Investigational New Drug (IND) status and has not received U.S. Food and Drug Administration (FDA) approval for any medical use. This means it is available primarily as a “research chemical,” carrying significant implications for public use. The lack of regulatory approval means there is no standardized quality control for products sold as NSI-189; their purity, dosage, or actual content cannot be guaranteed. Using such compounds without medical oversight can pose serious health risks due to unknown long-term effects and potential interactions with other medications or existing health conditions. Therefore, self-medication with NSI-189 is strongly discouraged.