VistaGen Therapeutics (VTGN) is a biotechnology company focused on improving treatments for patients with Major Depressive Disorder (MDD). The company is taking a different approach from all other therapies that exist today. Current therapies for MDD are standard antidepressants and atypical antipsychotics. VistaGen is taking a different route with its oral drug AV-101. It doesn’t even have to steer far away in terms of clinical development. That’s because the company is using a modified version of an FDA approved drug known as Ketamine. More about Ketamine will be explained below. Just know that if the current clinical trials are successful, VistaGen can move on to other indications as well.
Ketamine and AV-101
There are a lot of patients who have to cycle through many antidepressants before they find the right one. Think about that for a second. These patients with MDD are in serious need of medication to help them move on with their daily lives. Having to try out multiple treatments until one works is just terrible for these patients. Even then, patients go through first-line, second-line, and third-line of treatments. Sometimes they have to take these antidepressant treatments together with atypical antipsychotics. The problem now is that many patients who just take monotherapy antidepressants go through drug resistance (when patients are immune to the drug in question or it doesn’t work for them at all).
Ketamine was approved by the FDA back in the 1970s for anesthesia. Recent studies at Yale and the National Institute of Mental Health showed that ketamine relieved treatment-resistant MDD in 71% of patients within 24 hours. However, it it not suitable for long-term use, and also requires intravenous administration. The studies catalyzed interest in development of new antidepressants that are fundamentally different from current therapies.
VistaGen’s drug AV-101 is similar to ketamine in targeting NMDA and AMPA receptors in the brain. The mechanism of action of ketamine works first by entering the blood brain barrier. It targets the NMDA glutamate receptor of the brain, which then allows for the release of AMPA receptors. That’s when key connection by neurons are improved, thus improving clinical outcome. In essence, it acts through the AMPA dependent pathway. That ends up generating antidepressant effects. AV-101 intends to be safer by avoiding some of the negatives of ketamine (by inhibiting rather than blocking the NMDA receptor) and to be available in oral form.
