Evaluation of a novel soil-derived Mycobacterium as a nutritional supplement to promote stress resilience

Modified Project Summary/Abstract Section The National Institute of Mental Health projects that one in five U.S. adults experience a mental health disorder in a given year, with anxiety disorders being the most common, followed by major depressive disorder. Immunoregulation, i.e., a balanced expression of regulatory and effector T cells, is thought to be compromised in modern high-income settings due in part to reduced contact with commensal and environmentally derived bacteria, also known as “old friends”. Failed immunoregulation is thought to be one factor contributing to recent increases in chronic inflammatory disorders as well as stress-related psychiatric disorders in which inflammation is a risk factor, such as anxiety disorders. Mycobacteria Therapeutic Corporation’s (MTC) mission is to develop immunoregulatory strains of heat-killed mycobacteria for stress resilience and mental wellbeing. We are building off a body of over 25 years of impactful research in nonpathogenic, environmentally derived mycobacteria that have anti-inflammatory and immunoregulatory properties and have been shown to increase stress resilience in mice and rats as assessed by prevention of stress-induced increases in anxiety- and fear-like behavior. This proposal is a continuation of our funded Phase I STTR award where we isolated thirty novel strains of soil-derived mycobacteria that we subsequently screened with our in vitro screening assay to rank each novel strain for their immunoregulatory potential. From these results, we identified a lead strain of Mycobacterium (MTC 0012) that showed the highest immunoregulatory potential. MTC 0012 promoted stress-resilience by preventing stress-induced anxiety-like behavior in the inescapable stress/juvenile social exploration paradigm. Further pre-clinical and clinical development is required for the successful commercialization of MTC 0012. Here, we propose the following aim: 1) perform an oral dose-response experiment to determine the most effective dose of MTC 0012 to promote an immunoregulatory phenotype and stress resilience, as we previously demonstrated via s.c. administration. This study will provide critical data on the most effective dose for oral administration and provide a key steppingstone on MTC 0012’s path to successful commercialization. Following the completion of this study we will rapidly pursue further studies to assess safety via industry standard in vitro and in vivo toxicology studies (i.e OECD 471, 473, 474, and 408) and subsequent efficacy-based clinical testing via a sufficiently powered randomized, double-blind, placebo-controlled clinical trial.