Task Progress:
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The goal of this project was to support development of the first "Astrobiotic", designed to combat and/or treat cognitive or behavioral conditions and psychiatric disorders astronauts may experience during their journeys. Resources acquired via this solicitation were used to perform lead optimization on HOLO-101 -- a consortium of two human-derived strains which target the host GABAergic and inflammatory response -- in two rat models of stress and depression. The goals were twofold: (1) determine whether HOLO-1 could exhibit efficacy in two animal models of behavior, as compared to the positive control ketamine; and (2) if so, determine whether a single strain representative within HOLO-1 could exhibit the same effect.
Two animal models (rats) were used in this study. The first was the limited bedding and nesting model, which elicits early life stress and is well published to induce depressive- and anxiety-like behavior. Unfortunately, after significant effort in optimizing the model using published protocols and consulting with experts, the model was not seen to cause depressive- or anxiety-like behavior. We then moved on to a second model, known as social defeat, which we did find exhibited the anticipated phenotype. Excitingly, in this model we found HOLO-1 exhibited anti-depressant activity, as measured via the sucrose preference test.
Analysis is ongoing for a range of tissues collected throughout the study, including shotgun metagenomic sequencing of cecal contents and stool; serum, cecum, stool, and brain GABA levels; and RNAseq in cecum and brain tissues. Immunological profiling is ongoing in plasma samples. This analysis is expected to be completed in Q1 2021. We anticipate the intervention with HOLO-101 will be associated with increased systemic levels of GABA and/or increase GABAergic activity in some of the collected tissues.
Supported by additional Holobiome studies showing therapeutic potential of HOLO-1, these results encourage us to enter into manufacturing and human testing in 2022. Given the path-to-market is currently first planned as a consumer facing probiotic, and assuming strong safety profiles in humans, HOLO-1 may be available to the public in 2023.
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