Extended space missions place considerable demands upon human physiology. The Sovaris countermeasure effort is focused on development of countermeasures across a range of human physiologic challenges encountered in space. This includes,
- small molecule countermeasures
- neurophysiologic assessment and training tools
- training countermeasures.
Assessment of Human Physiologic and Molecular Adaptation in Complex Environments: Countermeasure Development
Sovaris uses non-hypothesis-driven methodologies to help identify the source of biological variance in humans exposed to the extreme environments of space flight or in human ground-based analogues to space flight. These methods allow us to approach a problem by searching for variance in gene, protein, or metabolite networks. Understanding this variance can direct us to understand novel mechanisms of action, novel therapeutic targets, and develop novel countermeasures. We search for similar variance in a range of neurophysiologic measures.
For example, Sovaris is part of NASA teams attempting to understand mechanisms, associated with the following:
- Ocular deterioration associated with space flight. In this case, Sovaris’ team is focused on understanding gene, protein, and metabolite networks in a human earth analogue, in order to better profile risk and develop countermeasures.
- Advanced physical training countermeasures. In this case, Sovaris’ team is focused on understanding gene, protein, and metabolite networks, to better understand the mechanisms associated with various advanced training technologies. One such technology utilizes 1) restricted muscle blood flow (compression) and physical loading (various exercise paradigms) to increase anabolic drive in humans exposed to extreme environments or in humans undergoing extreme training regimens. These methods are also being studied for their application to human medicine. The Sovaris Assessment and Countermeasures group is working with to build a molecular profile that will help explain the mechanism of action, as well as generate novel methods to further optimize the technology.
- Orthostatic intolerance. Sovaris is also collaborating on studies examining effects of microgravity on orthostatic intolerance in astronauts who return to earth gravity. Sovaris’ efforts are focused on identifying metabolic networks in simulation environments in an effort to describe mechanism of action and lay a foundation for countermeasure development.
Our neurophysiology assessment tools are aimed at improving human tolerance to extreme conditions. This platform of essential tools takes two forms. One is as a tool to assess the human response to challenging conditions, such as space flight, exposure to high altitudes, and extended duration missions. The other is to use our system for training, with the aim that individuals may better tolerate and thrive in these extreme conditions. Our neurophysiology platform is focused on autonomic regulation, maintaining efficiency of the coherent connection between the volitional and autonomic nervous system functions. It is also aimed at determining directionality within the neurophysiologic metrics, allowing us to better described neural processing under many different conditions of either performance or disease.
Assessment of Human Tissue Models as Surrogates for Human Assessment: Countermeasure Development
Sovaris uses non-hypothesis-driven methodologies to help identify the source of biological variance in human tissue models exposed to the extreme environments of space flight or ground-based analogues to space flight. The 3-dimensional tissue ‘omics platform allows us to study human tissue models when studying living humans is more difficult. These methods allow us to approach a problem by searching for variance in gene, protein, or metabolite networks in the 3-D human tissue analogues. Understanding this variance can direct us to understand novel mechanisms of action, novel therapeutic targets, and develop novel countermeasures.
For example, Sovaris is part of NASA teams attempting to understand mechanisms, associated with the following:
- Radiation effects associated with repeated suborbital space missions. In this case, Sovaris’ team is focused on understanding gene, protein, and metabolite networks, using 3-dimensional tissue models of human neural progenitor cells, peripheral blood monocytes, and other cells exposed repeatedly to suborbital altitudes. The goal is to identify individual risk profiles and develop countermeasures that make suborbital space flight safer and to enable improved human performance in the suborbital environment.
Space Radiation Countermeasures
See: Schmidt, MA, Goodwin, TJ (2013) Personalized Medicine in Human Space Flight: Using Omics Based Assessment to Develop Individualized Countermeasures that Enhance Astronaut Safety and Performance. Metabolomics DOI 10.1007/s11306-013-0556-3.
Maintaining Host Defenses Against Microbes During Space Flight
Previous research has shown that certain types of bacteria become more virulent in space. This virulence response may also occur across a spectrum of bacterial types that have not yet been studied. It is also apparent that viruses can become more virulent in the space environment. This is often associated with re-expression of latent viruses in the host, such as herpes virus and cytomegalovirus. It may also include other viruses not yet studied. While most space missions maintain a strong arsenal of anti-viral and anti-bacterial drugs, drug resistance and superbugs are an emergent and serious problem. To compound the dilemma, as microbial resistance has grown, the pipeline of new antimicrobial drugs has nearly dried up. This means that astronauts and space participants will have to take measures to maintain strong host defenses as one method to address the microbial threat in space.
Sovaris Aerospace is focused on a systems biology approach to building and maintaining host defenses in space flight conditions. This is linked to our Essential Input-Based Metabolomics and a range of features that influence the host-microbe dynamic. It also includes our neuroelectrophysiology platform (described briefly below). The small molecule initiative also has a number of candidates that address attachment of bacteria, such as MRSA. The platform further deploys candidates that inhibit common envelope viruses. Current work on viruses, such as H1N1, H3N2, H5N1, herpes simplex, and rhinovirus, suggest that our compounds influence viral attachment, limiting the ability of the virus to enter human cells.
Additional applications are noted below.
Maintaining Immune Surveillance in the Space Environment: Preventing Abnormal Cell Growth
A single study on the Columbia space shuttle mission revealed an unexpected finding. A 3-dimensional co-culture model of prostate cancer cells and bone cells was prepared on earth. One tissue model was flown on Columbia, while the other was maintained on earth. During the 16-day mission, three separate tumor masses formed in the model that was flown in space. In contrast, the control tissue model on earth developed no such tumor aggregates. This small study suggested that the space condition might pose a unique threat to abnormal cellular transformation, such as that found in cancer.
While the compelling study in this field did not include an intact immune system to suppress tumor growth, the phenomenon has caused medical researchers exploring long range space flight to begin investigating the phenomenon in more detail. Sovaris Aerospace is exploring small molecules that target the natural physiological responses that help our cells recognize and contain abnormal cell growth.
Maintaining Skeletal and Cardiac Muscle Function During and After Space Flight
Sovaris is working on small molecule countermeasures, as well as neurophysiology-based training methods to counter the significant demands on the cardiovascular and skeletal muscle systems.
Maintaining Cognitive Function During and After Space Flight
Sovaris is working on small molecule countermeasures, as well as neurophysiology-based training methods to counter the effects of space flight on memory and cognition.