Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) is one in a series of investigations designed to determine if administering an experimental agent preflight reduces the loss of bone associated with space flight. Humans and animals have been observed to lose bone mass during the reduced gravity of space flight. The sclerostin antibody is designed to inhibit the action of "sclerostin", a protein that is a key negative regulator of bone formation, bone mass and bone strength.Principal Investigator(s)
University of Colorado at Boulder, BioServe Space Technologies, Boulder, CO, United States
NASA Ames Research Center, Moffett Field, CA, United States
Amgen Research, Thousand Oaks, CA, United States
National Aeronautics and Space Administration (NASA)Sponsoring Organization
National Laboratory (NL)ISS Expedition Duration
March 2011 - September 2011
27/28Previous ISS Missions
A similar investigation, CBTM, flew round trip to the ISS on STS-108 during ISS Expedition 4. CBTM-2 flew round trip to the ISS on STS-118 during ISS Expedition 15. AEMs have flown on numerous space shuttle missions over the years.
Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) is part of a suite of investigations studying the ability of novel experimental agents to prevent disuse induced bone loss, and extend current knowledge about the effects of microgravity on the musculoskeletal system and the ability of a ground-based analog system (rodent hind limb suspension) to reproduce those effects in mice. The ultimate objective is to mitigate the risk for space-induced skeletal fragility associated with missions to low Earth orbit, and exploration destinations. If the sclerostin antibody proves successful in reducing space flight induced bone mass loss in mice, then it will demonstrate the potential for pharmacologic inhibition of sclerostin to be used in astronauts. Beyond the perils of microgravity, the findings may also provide novel insight into prevention and treatment of the skeletal fragility that can result from “skeletal disuse” in such conditions as immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury, and reduced physical activity. Eight to ten mice are flown in each of three Animal Enclosure Modules (AEMs) (http://flighthardware-spacebiosciences.arc.nasa.gov/) located on the space shuttle middeck. Half of the mice are given a preflight injection of a novel experimental bone forming agent, an antibody designed to inhibit the activity of the protein “sclerostin”. The remaining mice receive a placebo. Following the flight, a team of scientists, are studying various aspects of the structure, composition, strength, and cell and molecular nature of the bones from the flight and ground-based control mice. Bones from mice receiving the bone forming agent are compared to those receiving the placebo and are also compared to a ground control group, i.e., mice that were housed in AEM's on the ground during the flight.
This research is also expected to contribute data to the current body of research on microgravity effects on the skeletal, cardiovascular, and immune systems, liver and kidney function as well as other physiological systems through a tissue sharing program. Every effort will be made to harvest as many different samples and types of tissue from the mice as possible for other mission specific biomedical research. Positive results from this research may advance our understanding of mechanistic changes that occur in various physiological systems after exposure to microgravity and support overall efforts to reduce health risks to crewmembers. The investigations resulting from the CBTM-3 tissue sharing program are as follows:
If the novel bone forming agent proves successful in mitigating bone mass loss in-flight, this would demonstrate the potential application of pharmacologic sclerostin inhibition as a countermeasure for use in long-duration human space flight missions.Earth Applications
If the sclerostin antibody proves successful in reducing space flight induced bone mass loss, the results may point towards possible prevention and treatment of the bone loss that can result from “skeletal disuse” in such conditions as immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury, and reduced physical activity.
AEM's with eight to ten mice each are requested for a late load (Launch minus 72 to 24 hours) and to be removed postflight within four hours of landing. During flight the crew is requested to conduct a daily health check of the mice, i.e., a visual observation through the Lexan lid of the AEMs. Unusual appearances of the mice are to be reported as soon as possible.Operational Protocols
For this study nine week old female C57BL/6 mice are launched on the space shuttle. Flight mice are treated once with a placebo vehicle or the bone forming agent approximately 24 hours before launch. Ground control mice are treated in the same manner but with a 48 hour offset. Ground control mice are housed under the same environmental conditions (temperature, light/dark cycle, humidity, oxygen levels and carbon dioxide levels) as the flight mice. All mice receive the same full access to food and water. Upon return to Earth, the AEMs are returned to the research team for analysis. Body weight is also measured preflight and postflight. Statistical comparisons will be made between the treated and control mice.
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