PHILADELPHIA, November 19, 2021 (GLOBE NEWSWIRE) – Enterin Inc., a Philadelphia-based privately held, clinical-stage biopharmaceutical company pioneering novel treatments for neurodegenerative and metabolic diseases, announces the publication in Scientific Reports of an article titled “Identification of Sensory signals from antidepressants evoked by SSRIs by decoding vagus nerve activity. “
The vagus nerve is the main neural connection between the gut and the brain. A large number of sensory signals from the gut are captured by the enteric nervous system (ENS) and transmitted to the brain via the vagus nerve. As a result, damage to either the ENS or the vagus nerve can have significant gastrointestinal consequences as well as neuropsychiatric consequences.
Serotonin (5-hydroxytryptamine; 5-HT) is an important neurotransmitter in both the central nervous system (CNS) and the ENS. In addition, 95% of the body’s serotonin is produced in the gastrointestinal tract. Serotonin is involved in gastrointestinal functions such as neurogenesis, epithelial repair, gastrointestinal secretions, and intestinal motility. Serotonin also has an excitatory effect on the vagus nerve, regulating important CNS functions such as appetite, sleep and mood.
Oral selective serotonin reuptake inhibitors (SSRIs) such as sertraline or fluoxetine exert their antidepressant action by stimulating the vagus nerve (at least in mice) and cutting the vagus nerve abolishes the antidepressant effect . Unlike SSRIs, the antidepressant effect of bupropion, a dopamine and norepinephrine reuptake inhibitor, is not mediated by the vagus nerve, and the effect is not abolished by vagotomy.
While vagal nerve fibers are known to be stimulated by SSRIs, it is not clear exactly how they encode a specific “antidepressant signal” (as opposed to a depressant signal).
This study by West and colleagues at the Brain Body Institute at McMasters University and scientists at Enterin Inc., using single vagal fiber recordings, demonstrated that SSRIs evoke unique trigger patterns, consisting of an increase in the frequency of the spikes, the duration of the bursts, the interval of the intra-burst spikes and a decrease in the duration of the interval between the bursts. This firing pattern was significantly different from the firing pattern produced by bupropion, which caused an increase in all four firing parameters.
Pharmacological silencing of ENS cells abolished the “antidepressant code” induced by the application of sertraline, indicating that the effect of sertraline on the vagus nerve is mediated by ENS.
“Our work demonstrates that electrical signals generated by the nervous system in the gut can influence complex behavioral states,” says Wolfgang Kunze, Ph.D., lead author of the study. “Our discovery identifies, for the first time, a unique gut-brain signal carried by the vagus nerve that can improve a specific neuropsychiatric symptom. We believe our research will ultimately lead to the development of more effective treatments for neurological diseases.”
Squalamine, a shark-derived aminosterol discovered by Enterin co-founder and CSO, Michael Zasloff, MD., Ph.D., produced an antidepressant code comparable to that evoked by sertraline. A synthetic version of this compound, ENT-01, is currently in Phase 2 clinical trials in patients with Parkinson’s disease.
Dr Zasloff commented: “We have recently shown that squalamine inhibits the monoamine reuptake transporter, inhibiting the reuptake of serotonin as well as dopamine and norepinephrine. Preventing the reuptake of serotonin in the gastrointestinal tract would increase the amount of serotonin available to stimulate ENS. and vague and would explain the serotonergic signal observed in the single fiber recordings. “
According to Enterin Co-Founder and Marketing Director, Denise Barbut, MD., FRCP., “The serotonergic vagal signal observed after the application of squalamine may explain the improvement in depression, dementia and psychosis that we experience. observed in preliminary studies in patients with Parkinson’s disease. “She added that Enterin is initiating further clinical studies focusing specifically on PD-related dementia and PD-related psychosis.
The document is available at: https://www.nature.com/articles/s41598-021-00615-w
About Enterin Inc.
Enterin Inc. is the first company to develop new compounds that repair the dysfunctional gut-brain axis in patients with neurodegenerative diseases. Enterin Inc. is a pioneer in the medical community’s understanding of the link between infections, ENS dysfunction and the onset and progression of neurodegenerative diseases. Enterin’s main compound, ENT-01, displaces alpha-synuclein (αS) aggregates bound to the membrane of ENS nerve cells and improves neural signaling between the gut and the brain. Enterin Inc. is now advancing ENT-01 into Phase 2 clinical trials with the goal of reversing the neurological symptoms of Parkinson’s disease. The second compound, ENT-03, increases insulin sensitivity by acting in the brain and acutely normalizes blood sugar levels in diabetic mice. ENT-03 is developed for the treatment of diabetes, obesity and Alzheimer’s disease. Studies in humans are expected to start in the first half of 2022.
For more information, please visit www.enterininc.com.
Image 1: Enterin Inc
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